Biotweeps conference:
RNA sequencing-based cell proliferation analysis across 19 cancers identifies a subset of proliferation-informative cancers with a common survival signature
This document discusses modern treatment strategies for diffuse large B-cell lymphoma (DLBCL). It summarizes that DLBCL is molecularly distinct diseases with different biological characteristics and outcomes. Targeted therapies like ibrutinib and lenalidomide show promise for the activated B-cell (ABC) subtype of DLBCL. Monitoring circulating tumor DNA is presented as a very promising tool for early detection of treatment failure or recurrence, which can allow for pre-emptive treatment changes or early intervention.
The document summarizes research using chick embryo models to study cancer metastasis. It describes several advantages of the chick embryo model, including its ability to support rapid growth of xenografted human tumor cells. Several chick embryo cancer models are outlined, including models for spontaneous metastasis, analyzing tumor cell interactions with vasculature, and studying invasion and extravasation. Examples are given of studies using these models to analyze tumor growth and metastasis of various cancer cell lines and effects of potential therapeutics.
The document summarizes research on identifying cells that initiate human malignant melanoma (MMICs). The key findings are:
1. ABCB5, an ATP-binding cassette transporter protein, is expressed in MMICs and closely associated with advanced melanoma.
2. ABCB5+ melanoma cells were able to initiate tumor formation in mice, while ABCB5- cells did not, indicating ABCB5+ cells drive melanoma progression.
3. Blocking ABCB5 using an antibody inhibited tumor growth in mice xenografts, suggesting ABCB5 is a potential therapeutic target for treating advanced melanoma.
This document summarizes the use of the nematode C. elegans as a model organism for studying human diseases. It discusses how CRISPR/Cas9 can be used to introduce disease-related mutations into C. elegans to model retinitis pigmentaria, cancer, and responses to chemotherapy. Drug screens and RNAi screens in these mutant worms have identified genetic modifiers and potential drug targets for treating human diseases. The small size, rapid life cycle, and genetic tractability of C. elegans make it a valuable pre-clinical model for validating targets and precision medicines before testing in mammalian systems.
The connection between germline risk variants and somatic mutation patterns i...David Goode
Platform session presentation at the 2016 American Society of Human Genetics Conference in Vancouver by Dr. David Goode, Peter MacCallum Cancer Centre, Melbourne, Australia.
This document summarizes an RNA-Seq study of Semaphorin gene expression in breast cancer cells. The study found:
1) RNA-Seq of MCF-7 breast cancer cells identified over 14,000 expressed genes including Semaphorin genes and their receptors.
2) A novel alternatively spliced transcript of SEMA3F was predicted from RNA-Seq data and validated, skipping exon 16 (SEMA3FΔ16).
3) SEMA3F expression was significantly upregulated in breast tumor tissues compared to healthy tissues, suggesting it may be a potential biomarker for breast cancer.
Widespread human T cell receptor beta variable gene polymorphism: implication...Thermo Fisher Scientific
Polymorphism within the TCRB variable gene (TRBV) has been linked to chronic autoimmune diseases such as Type 1 Diabetes, Rheumatoid Arthritis, Psoriatic Arthritis, Multiple Sclerosis and Asthma (1-8), and may also be mechanistically linked to immune mediated adverse events (IMAEs) during immunotherapy (9-11). Here we use the Ion-AmpliSeq™ Immune Repertoire Plus TCRB assay to evaluate TRBV gene polymorphism in a group of 85 Caucasians with melanoma. The assay provides coverage of all three CDR domains to enable detection of TRBV polymorphism. We find evidence of extensive genetic diversity within the TRBV gene, including 15 nonsynonymous variants that are absent from the IMGT database (12). TRBV gene allele typing may provide rich biomarker information for the prediction of IMAEs and chronic autoimmune disease.
This document discusses modern treatment strategies for diffuse large B-cell lymphoma (DLBCL). It summarizes that DLBCL is molecularly distinct diseases with different biological characteristics and outcomes. Targeted therapies like ibrutinib and lenalidomide show promise for the activated B-cell (ABC) subtype of DLBCL. Monitoring circulating tumor DNA is presented as a very promising tool for early detection of treatment failure or recurrence, which can allow for pre-emptive treatment changes or early intervention.
The document summarizes research using chick embryo models to study cancer metastasis. It describes several advantages of the chick embryo model, including its ability to support rapid growth of xenografted human tumor cells. Several chick embryo cancer models are outlined, including models for spontaneous metastasis, analyzing tumor cell interactions with vasculature, and studying invasion and extravasation. Examples are given of studies using these models to analyze tumor growth and metastasis of various cancer cell lines and effects of potential therapeutics.
The document summarizes research on identifying cells that initiate human malignant melanoma (MMICs). The key findings are:
1. ABCB5, an ATP-binding cassette transporter protein, is expressed in MMICs and closely associated with advanced melanoma.
2. ABCB5+ melanoma cells were able to initiate tumor formation in mice, while ABCB5- cells did not, indicating ABCB5+ cells drive melanoma progression.
3. Blocking ABCB5 using an antibody inhibited tumor growth in mice xenografts, suggesting ABCB5 is a potential therapeutic target for treating advanced melanoma.
This document summarizes the use of the nematode C. elegans as a model organism for studying human diseases. It discusses how CRISPR/Cas9 can be used to introduce disease-related mutations into C. elegans to model retinitis pigmentaria, cancer, and responses to chemotherapy. Drug screens and RNAi screens in these mutant worms have identified genetic modifiers and potential drug targets for treating human diseases. The small size, rapid life cycle, and genetic tractability of C. elegans make it a valuable pre-clinical model for validating targets and precision medicines before testing in mammalian systems.
The connection between germline risk variants and somatic mutation patterns i...David Goode
Platform session presentation at the 2016 American Society of Human Genetics Conference in Vancouver by Dr. David Goode, Peter MacCallum Cancer Centre, Melbourne, Australia.
This document summarizes an RNA-Seq study of Semaphorin gene expression in breast cancer cells. The study found:
1) RNA-Seq of MCF-7 breast cancer cells identified over 14,000 expressed genes including Semaphorin genes and their receptors.
2) A novel alternatively spliced transcript of SEMA3F was predicted from RNA-Seq data and validated, skipping exon 16 (SEMA3FΔ16).
3) SEMA3F expression was significantly upregulated in breast tumor tissues compared to healthy tissues, suggesting it may be a potential biomarker for breast cancer.
Widespread human T cell receptor beta variable gene polymorphism: implication...Thermo Fisher Scientific
Polymorphism within the TCRB variable gene (TRBV) has been linked to chronic autoimmune diseases such as Type 1 Diabetes, Rheumatoid Arthritis, Psoriatic Arthritis, Multiple Sclerosis and Asthma (1-8), and may also be mechanistically linked to immune mediated adverse events (IMAEs) during immunotherapy (9-11). Here we use the Ion-AmpliSeq™ Immune Repertoire Plus TCRB assay to evaluate TRBV gene polymorphism in a group of 85 Caucasians with melanoma. The assay provides coverage of all three CDR domains to enable detection of TRBV polymorphism. We find evidence of extensive genetic diversity within the TRBV gene, including 15 nonsynonymous variants that are absent from the IMGT database (12). TRBV gene allele typing may provide rich biomarker information for the prediction of IMAEs and chronic autoimmune disease.
This study examines the role of the long non-coding RNA LINC00337 in breast cancer (BCa). The researchers found that LINC00337 promotes BCa cell growth and migration by enhancing the effects of tumor-associated macrophages (TAMs). Overexpression of LINC00337 increased tumor formation in mice, while silencing LINC00337 inhibited tumor growth. LINC00337 upregulated levels of cytokines like IL-13 and CCL2 known to promote the tumor-promoting M2 phenotype of TAMs. This suggests LINC00337 may regulate TAM polarization to support BCa progression.
Insights into the tumor microenvironment and therapeutic T cell manufacture r...Thermo Fisher Scientific
TCRβ immune repertoire analysis by next-generation sequencing is emerging as a valuable tool for research studies of the tumor microenvironment and potential immune responses to cancer immunotherapy1-4. Here we describe a multiplex PCR-based TCRβ sequencing assay (Ion AmpliSeqTM Immune Repertoire Assay Plus – TCRβ) that leverages Ion AmpliSeq library construction chemistry and the long read capability of the Ion S5 530TM chip to provide coverage of all three CDR domains of the human TCRβ chain. We demonstrate use of the assay to evaluate tumor-infiltrating T cell repertoire features and monitor manufacture of therapeutic T cells.
This document discusses antibody-drug conjugates (ADCs) for treating diffuse large B-cell lymphoma (DLBCL). It summarizes early ADC technologies from the 1970s-1990s using murine antibodies and discusses failed phase III studies of gemtuzumab ozogamicin. The document also reviews lessons learned from myelotarg and discusses newer ADCs targeting CD22 and CD79b that show promise, particularly in refractory DLBCL. It concludes that continued development of novel drugs, targets, linkers, and combination therapies can help move ADCs forward as effective lymphoma therapies.
This document summarizes a study examining the role of CD44 variant 9 (CD44v9) and Muc18 expression in prostate cancer invasion and metastasis. The study found that prostate cancer tissues and metastases overexpressed CD44v7-v10 isoforms compared to benign tissue. Silencing CD44v9 expression in cultured prostate cancer cells significantly reduced invasiveness into Matrigel, while silencing Muc18 had a smaller effect. A more invasive cell line, Gsa, was also found to overexpress CD44v9. The results suggest that prostate cancer invasion is more influenced by CD44v9 expression than by Muc18 expression.
NSA Diagnostic Laboratory has been operating since 1958, founded by Prof. Nasseh Amin. NSA is considered as one of the most advanced labs in Egypt. Maintaining personalized services for its stakeholders, as well as the main role of the lab "Diagnosis"
NSA Diagnostic Laboratory operates through two different segments.
Firstly, a group of stand-alone labs located at prime locations all over Egypt, with the latest and up to date equipments.
Secondly, being the backbone of well reputed hospitals and some polyclinics where NSA is the lab that is responsible for all medical testing there, serving all our patients with class A quality.
Our main focus is delivering quality care and with Cost-value return. NSA plays a key role in improving the health of many Egyptians, by providing access to quality service for more than 200,000 patients annually.
This document provides an agenda for a lecture on copy number variations (CNV) and their role in cancer development and pharmacogenetics. It begins with an introduction to CNVs, including definitions and mechanisms for their creation. It then discusses how CNVs can contribute to disease susceptibility and notes their role in directly influencing cancer cell genomes. The document outlines how common and rare CNVs may serve as "first hits" to the tumor genome or influence cancer risk. It provides some examples of specific cancers associated with CNVs and discusses how pharmacogenetics focuses on CNV effects in cancer treatment for drugs like tamoxifen and irinotecan. The document concludes by noting the promising potential for further discovery regarding C
This study identified BRAF mutations in patients with hairy cell leukemia (HCL). The BRAF V600E mutation was present in all HCL patients tested, leading to overactive BRAF signaling and increased cell proliferation. Immunohistological and Western Blot tests found constitutive activation of the RAF-MEK-ERK pathway in HCL cells. A BRAF inhibitor reduced phosphorylation of MEK and ERK, indicating BRAF drives HCL pathogenesis. Identifying this genetic mutation improves understanding of HCL and could inform future treatment development.
Post-transplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication of chronic immunosuppression in organ transplant recipients. It is most commonly seen as non-Hodgkin's lymphomas that are usually of B-cell origin. PTLD is caused by B cell proliferation induced by Epstein-Barr virus infection in the setting of immunosuppression. The degree of immunosuppression, EBV serostatus, time since transplant, and HLA matching all influence the risk of developing PTLD. Biopsy of lymph nodes and other involved tissues is important for diagnosis, while treatment involves reducing immunosuppression and using rituximab or chemotherapy.
Cystic fibrosis and thrombophilic mutationsMarek Turnovec
Lecture "Cystic fibrosis and thrombophilic mutations", that I had during optional subject Reproductive medicine and reproductive genetics on 2nd Medical Faculty of Charles University in Prague on 3rd May 2011.
This document discusses cancer and genetic influences. It defines cancer as uncontrolled cell proliferation that occurs due to an imbalance in cellular proliferation and death. Cancer is caused by mutations in genes controlling processes like proliferation, the cell cycle, and programmed cell death. The document summarizes the major types of cancer and characteristics of cancer cells. It describes how cancer can be influenced by genetics, with some forms having a higher incidence in families. Cancer is considered a genetic disease caused by mutations in genes regulating cell growth and death. Key genes involved include oncogenes, tumor suppressors, and genes responsible for DNA repair. Specific oncogenes discussed are RAS, RET, MET, and MYC. RAS family proto-oncogenes are described in
Tumor Mutational Load assessment of FFPE samples using an NGS based assayThermo Fisher Scientific
Understanding the molecular determinants of response to immune checkpoint blockade inhibitors is a critical unmet need for translational oncology research. Research tools to characterize the mutational landscape of cancers may potentially help identify predictive biomarkers for immuno-therapy that can be tested in future studies. Herein, we describe a targeted Ion AmpliSeq assay to determine the mutational load and signature of cancer research samples.
The document discusses mechanisms of tumor suppressor genes and their role in cancer development. It describes how tumor suppressor genes like RB-1, p53, and BRCA1/2 normally regulate cell cycle and DNA repair but are inactivated in cancer through mutations or deletions. Viruses can also interact with cell cycle pathways by binding to proteins like Rb and p53. The document lists several tumor suppressor genes and the cancers they are associated with. It also discusses using oncolytic viruses to selectively target and kill cancer cells.
A recellularized human colon model identifies cancer driver genesShamir Montazid
This document describes the creation of an ex vivo human colon model to study colorectal cancer (CRC). Researchers (1) decellularized human colon tissue to generate an extracellular matrix scaffold, (2) seeded the scaffold with different colon cell types to recreate the tissue architecture, and (3) validated that the model resembled native human colon. CRC was then modeled by transforming seeded cells and inhibiting tumor suppressors. A forward genetic screen using transposons identified 38 candidate driver genes of metastasis. The ex vivo model enables rapid and low-cost CRC studies in near-physiological conditions.
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
Talimogene (T-VEC) : virotherapy in melanomaLorenzo Alonso
1) Talimogene laherparepepvec (T-VEC) is an oncolytic virus that has been genetically modified from herpes simplex virus type 1 to selectively replicate in tumor cells.
2) In a Phase III clinical trial, T-VEC showed a significantly higher durable response rate compared to GM-CSF in treating unresectable stage IIIB-IV melanoma with minimal side effects.
3) T-VEC is the first oncolytic virus to demonstrate efficacy in a Phase III trial, showing promise as a new treatment approach by killing tumor cells and inducing anti-tumor immune responses.
Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011...Lymphoma Support Ireland
This document summarizes key information from a presentation on the treatment of lymphoma. It discusses:
1) The classification, incidence, and etiology of both Hodgkin's and non-Hodgkin's lymphomas.
2) Updates on treatment approaches for different lymphoma subtypes including chemotherapy regimens, monoclonal antibodies, and stem cell transplantation.
3) Results from clinical trials evaluating new agents and regimens for indolent non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, T-cell lymphomas, and relapsed Hodgkin's lymphoma.
This document describes a case study of preimplantation genetic diagnosis (PGD) performed on a breast cancer patient carrying a novel genomic deletion in the BRCA2 gene. Researchers first used single sperm haplotyping on the patient's carrier brother to establish linkage to the mutation. They then used BLAST analysis to locate putative hairpin structures in the genome and PCR screening to identify a 2,596 bp deletion in BRCA2 involving exons 15-16. PGD was performed using both direct mutation detection and linkage analysis to avoid misdiagnosis from recombination. This identified unaffected embryos, one of which was transferred, resulting in a live birth.
1) Bacteria can contribute to carcinogenesis through chronic inflammation and by producing genotoxins. Chronic inflammation and activation of NF-kB helps cancer cells overcome barriers to tumor development.
2) Epidemiological and animal studies provide evidence that bacteria like H. pylori and Salmonella that cause chronic inflammation increase cancer risk by inducing cytokines like IL-1β and TNFα. Blocking NF-kB reduces colorectal cancer progression in mouse models.
3) Bacterial toxins such as CagA from H. pylori and cytolethal distending toxin (CDT) directly cause DNA damage and genomic instability, contributing to mutations and tumor development in vitro and in vivo mouse models.
Dr. Manuel Hidalgo - Simposio Internacional ' Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
This document summarizes new approaches for head and neck cancer, including robotic surgery, proton radiotherapy, biomarkers like HPV and PD-L1 status, genomic profiling, and immunotherapy like nivolumab and pembrolizumab. It shows that immunotherapy such as nivolumab has better outcomes for HPV-positive head and neck cancer patients compared to standard chemotherapy. PD-L1 expression is also associated with better outcomes from pembrolizumab and nivolumab treatment. Combining cetuximab with chemotherapy improves survival compared to chemotherapy alone in recurrent/metastatic head and neck cancer. Pembrolizumab demonstrates superior overall survival compared to standard of care for recurrent/metastatic head and neck
This study examines the role of the long non-coding RNA LINC00337 in breast cancer (BCa). The researchers found that LINC00337 promotes BCa cell growth and migration by enhancing the effects of tumor-associated macrophages (TAMs). Overexpression of LINC00337 increased tumor formation in mice, while silencing LINC00337 inhibited tumor growth. LINC00337 upregulated levels of cytokines like IL-13 and CCL2 known to promote the tumor-promoting M2 phenotype of TAMs. This suggests LINC00337 may regulate TAM polarization to support BCa progression.
Insights into the tumor microenvironment and therapeutic T cell manufacture r...Thermo Fisher Scientific
TCRβ immune repertoire analysis by next-generation sequencing is emerging as a valuable tool for research studies of the tumor microenvironment and potential immune responses to cancer immunotherapy1-4. Here we describe a multiplex PCR-based TCRβ sequencing assay (Ion AmpliSeqTM Immune Repertoire Assay Plus – TCRβ) that leverages Ion AmpliSeq library construction chemistry and the long read capability of the Ion S5 530TM chip to provide coverage of all three CDR domains of the human TCRβ chain. We demonstrate use of the assay to evaluate tumor-infiltrating T cell repertoire features and monitor manufacture of therapeutic T cells.
This document discusses antibody-drug conjugates (ADCs) for treating diffuse large B-cell lymphoma (DLBCL). It summarizes early ADC technologies from the 1970s-1990s using murine antibodies and discusses failed phase III studies of gemtuzumab ozogamicin. The document also reviews lessons learned from myelotarg and discusses newer ADCs targeting CD22 and CD79b that show promise, particularly in refractory DLBCL. It concludes that continued development of novel drugs, targets, linkers, and combination therapies can help move ADCs forward as effective lymphoma therapies.
This document summarizes a study examining the role of CD44 variant 9 (CD44v9) and Muc18 expression in prostate cancer invasion and metastasis. The study found that prostate cancer tissues and metastases overexpressed CD44v7-v10 isoforms compared to benign tissue. Silencing CD44v9 expression in cultured prostate cancer cells significantly reduced invasiveness into Matrigel, while silencing Muc18 had a smaller effect. A more invasive cell line, Gsa, was also found to overexpress CD44v9. The results suggest that prostate cancer invasion is more influenced by CD44v9 expression than by Muc18 expression.
NSA Diagnostic Laboratory has been operating since 1958, founded by Prof. Nasseh Amin. NSA is considered as one of the most advanced labs in Egypt. Maintaining personalized services for its stakeholders, as well as the main role of the lab "Diagnosis"
NSA Diagnostic Laboratory operates through two different segments.
Firstly, a group of stand-alone labs located at prime locations all over Egypt, with the latest and up to date equipments.
Secondly, being the backbone of well reputed hospitals and some polyclinics where NSA is the lab that is responsible for all medical testing there, serving all our patients with class A quality.
Our main focus is delivering quality care and with Cost-value return. NSA plays a key role in improving the health of many Egyptians, by providing access to quality service for more than 200,000 patients annually.
This document provides an agenda for a lecture on copy number variations (CNV) and their role in cancer development and pharmacogenetics. It begins with an introduction to CNVs, including definitions and mechanisms for their creation. It then discusses how CNVs can contribute to disease susceptibility and notes their role in directly influencing cancer cell genomes. The document outlines how common and rare CNVs may serve as "first hits" to the tumor genome or influence cancer risk. It provides some examples of specific cancers associated with CNVs and discusses how pharmacogenetics focuses on CNV effects in cancer treatment for drugs like tamoxifen and irinotecan. The document concludes by noting the promising potential for further discovery regarding C
This study identified BRAF mutations in patients with hairy cell leukemia (HCL). The BRAF V600E mutation was present in all HCL patients tested, leading to overactive BRAF signaling and increased cell proliferation. Immunohistological and Western Blot tests found constitutive activation of the RAF-MEK-ERK pathway in HCL cells. A BRAF inhibitor reduced phosphorylation of MEK and ERK, indicating BRAF drives HCL pathogenesis. Identifying this genetic mutation improves understanding of HCL and could inform future treatment development.
Post-transplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication of chronic immunosuppression in organ transplant recipients. It is most commonly seen as non-Hodgkin's lymphomas that are usually of B-cell origin. PTLD is caused by B cell proliferation induced by Epstein-Barr virus infection in the setting of immunosuppression. The degree of immunosuppression, EBV serostatus, time since transplant, and HLA matching all influence the risk of developing PTLD. Biopsy of lymph nodes and other involved tissues is important for diagnosis, while treatment involves reducing immunosuppression and using rituximab or chemotherapy.
Cystic fibrosis and thrombophilic mutationsMarek Turnovec
Lecture "Cystic fibrosis and thrombophilic mutations", that I had during optional subject Reproductive medicine and reproductive genetics on 2nd Medical Faculty of Charles University in Prague on 3rd May 2011.
This document discusses cancer and genetic influences. It defines cancer as uncontrolled cell proliferation that occurs due to an imbalance in cellular proliferation and death. Cancer is caused by mutations in genes controlling processes like proliferation, the cell cycle, and programmed cell death. The document summarizes the major types of cancer and characteristics of cancer cells. It describes how cancer can be influenced by genetics, with some forms having a higher incidence in families. Cancer is considered a genetic disease caused by mutations in genes regulating cell growth and death. Key genes involved include oncogenes, tumor suppressors, and genes responsible for DNA repair. Specific oncogenes discussed are RAS, RET, MET, and MYC. RAS family proto-oncogenes are described in
Tumor Mutational Load assessment of FFPE samples using an NGS based assayThermo Fisher Scientific
Understanding the molecular determinants of response to immune checkpoint blockade inhibitors is a critical unmet need for translational oncology research. Research tools to characterize the mutational landscape of cancers may potentially help identify predictive biomarkers for immuno-therapy that can be tested in future studies. Herein, we describe a targeted Ion AmpliSeq assay to determine the mutational load and signature of cancer research samples.
The document discusses mechanisms of tumor suppressor genes and their role in cancer development. It describes how tumor suppressor genes like RB-1, p53, and BRCA1/2 normally regulate cell cycle and DNA repair but are inactivated in cancer through mutations or deletions. Viruses can also interact with cell cycle pathways by binding to proteins like Rb and p53. The document lists several tumor suppressor genes and the cancers they are associated with. It also discusses using oncolytic viruses to selectively target and kill cancer cells.
A recellularized human colon model identifies cancer driver genesShamir Montazid
This document describes the creation of an ex vivo human colon model to study colorectal cancer (CRC). Researchers (1) decellularized human colon tissue to generate an extracellular matrix scaffold, (2) seeded the scaffold with different colon cell types to recreate the tissue architecture, and (3) validated that the model resembled native human colon. CRC was then modeled by transforming seeded cells and inhibiting tumor suppressors. A forward genetic screen using transposons identified 38 candidate driver genes of metastasis. The ex vivo model enables rapid and low-cost CRC studies in near-physiological conditions.
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
Talimogene (T-VEC) : virotherapy in melanomaLorenzo Alonso
1) Talimogene laherparepepvec (T-VEC) is an oncolytic virus that has been genetically modified from herpes simplex virus type 1 to selectively replicate in tumor cells.
2) In a Phase III clinical trial, T-VEC showed a significantly higher durable response rate compared to GM-CSF in treating unresectable stage IIIB-IV melanoma with minimal side effects.
3) T-VEC is the first oncolytic virus to demonstrate efficacy in a Phase III trial, showing promise as a new treatment approach by killing tumor cells and inducing anti-tumor immune responses.
Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011...Lymphoma Support Ireland
This document summarizes key information from a presentation on the treatment of lymphoma. It discusses:
1) The classification, incidence, and etiology of both Hodgkin's and non-Hodgkin's lymphomas.
2) Updates on treatment approaches for different lymphoma subtypes including chemotherapy regimens, monoclonal antibodies, and stem cell transplantation.
3) Results from clinical trials evaluating new agents and regimens for indolent non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, T-cell lymphomas, and relapsed Hodgkin's lymphoma.
This document describes a case study of preimplantation genetic diagnosis (PGD) performed on a breast cancer patient carrying a novel genomic deletion in the BRCA2 gene. Researchers first used single sperm haplotyping on the patient's carrier brother to establish linkage to the mutation. They then used BLAST analysis to locate putative hairpin structures in the genome and PCR screening to identify a 2,596 bp deletion in BRCA2 involving exons 15-16. PGD was performed using both direct mutation detection and linkage analysis to avoid misdiagnosis from recombination. This identified unaffected embryos, one of which was transferred, resulting in a live birth.
1) Bacteria can contribute to carcinogenesis through chronic inflammation and by producing genotoxins. Chronic inflammation and activation of NF-kB helps cancer cells overcome barriers to tumor development.
2) Epidemiological and animal studies provide evidence that bacteria like H. pylori and Salmonella that cause chronic inflammation increase cancer risk by inducing cytokines like IL-1β and TNFα. Blocking NF-kB reduces colorectal cancer progression in mouse models.
3) Bacterial toxins such as CagA from H. pylori and cytolethal distending toxin (CDT) directly cause DNA damage and genomic instability, contributing to mutations and tumor development in vitro and in vivo mouse models.
Dr. Manuel Hidalgo - Simposio Internacional ' Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
This document summarizes new approaches for head and neck cancer, including robotic surgery, proton radiotherapy, biomarkers like HPV and PD-L1 status, genomic profiling, and immunotherapy like nivolumab and pembrolizumab. It shows that immunotherapy such as nivolumab has better outcomes for HPV-positive head and neck cancer patients compared to standard chemotherapy. PD-L1 expression is also associated with better outcomes from pembrolizumab and nivolumab treatment. Combining cetuximab with chemotherapy improves survival compared to chemotherapy alone in recurrent/metastatic head and neck cancer. Pembrolizumab demonstrates superior overall survival compared to standard of care for recurrent/metastatic head and neck
This document discusses tumor markers and their use in monitoring tumor response to therapy. It provides information on different types of tumor markers including proteins, enzymes, hormones, genetic markers and circulating tumor cells. Ideal tumor markers are highly sensitive and specific, correlate with tumor stage and prognosis, and can be used for screening, diagnosis, prognosis, monitoring treatment and detecting recurrence. Examples discussed include CEA, AFP, PSA, CA125 and circulating tumor cells. The Oncotype DX 21-gene recurrence score test and tissue polypeptide specific antigen are also summarized.
1) The document discusses workup, classification, prognostic factors, and treatment approaches for non-Hodgkin lymphoma. It covers topics such as immunohistochemistry panels, cell morphology, genetic markers, and clinical staging systems.
2) Treatment recommendations are provided for different subtypes and stages of NHL, including chemotherapy regimens and use of radiation therapy. Factors like tumor bulk and response to initial treatment are considered for determining subsequent treatment steps.
3) Guidelines for management of refractory or relapsed NHL address options like high-dose chemotherapy, radiation, second-line chemotherapy regimens, clinical trials, and autologous stem cell transplant.
The document discusses comprehensive genomic profiling (CGP) of solid tumors. It provides examples of genomic alterations that can be detected by CGP in various cancer types, including NSCLC, gliomas, and others. It describes how CGP interrogates many genes through next-generation sequencing to detect mutations, fusions, and other alterations that may be targeted with specific therapies or provide prognostic information.
This document summarizes updated overall survival (OS) data from the IMpower150 study, which evaluated the combination of atezolizumab, bevacizumab, and chemotherapy compared to chemotherapy plus bevacizumab alone in previously untreated non-squamous non-small cell lung cancer. Baseline characteristics were balanced across study arms. Statistically significant and clinically meaningful improvements in progression-free survival with the triple combination were previously reported and continued with additional follow-up. This presentation focuses on interim OS data in the overall study population and key subgroups.
Dr. José Baselga - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
This document discusses genomic oncology and personalized medicine, using lung cancers as a model. It summarizes several key technologies that enable genomic oncology like cDNA microarrays, array CGH, and next generation sequencing. It provides examples of how these technologies have been used to classify cancers like diffuse large B-cell lymphoma and myelodysplastic syndrome, and identify genetic mutations that can guide targeted therapies for cancers like EGFR-mutated lung cancer.
This is needs to be updated as new Biomarkers and Dx antibodies come into existence in remarkable numbers every day! You have to construct an algorithm based on your need and availability of antibodies. Selection of Antibodies for the algorithm also depends on your ability to recognize the characterization of the specific antibody.
The document discusses the use of diagnostic algorithms and antibody panels to identify tumor types through immunohistochemistry (IHC). It provides examples of algorithms that use sequential testing of antibodies to differentiate between common tumor types like carcinoma vs sarcoma, or to identify the primary origin of a metastatic tumor. The algorithms aim to increase diagnostic accuracy and guide treatment by narrowing down the possible tumor types. Key details about specific antibodies, their targets, and staining patterns are also presented.
Comprehensive molecular characterization of gastric adenocarcinoma
The Cancer Genome Atlas Research Network ( TCGA)
Nature, July 2014
JC, by
Mohsin Maqbool, AIIMS
The document discusses how cancer genomics is transforming cancer diagnosis. Next-generation sequencing technologies are enabling whole genome and exome sequencing of tumors at lower costs. This allows comprehensive genomic profiling of cancers to detect mutations, rearrangements, and biomarkers that provide diagnostic, prognostic and treatment information. However, challenges remain around technology, costs, data analysis and clinical integration. Pathologists will need to adapt training and integrate genomic data into diagnostic reporting to realize the potential of cancer genomics.
Tratamiento inicial de mNSCLC: visión panorámicaMauricio Lema
The document provides an overview of the initial treatment of metastatic non-small cell lung cancer. It discusses the importance of establishing an accurate diagnosis and biomarker testing through biopsy to determine histologic subtype and the presence of mutations like EGFR, ALK, ROS1, and BRAF. For patients with actionable mutations like EGFR mutations, targeted therapies like afatinib are recommended as the standard first-line treatment based on results from the LUX-Lung 3 and LUX-Lung 6 studies that showed improved progression-free survival compared to platinum-based chemotherapy.
This document summarizes key information from 1,812 cancer research abstracts analyzed on the BioTrack platform. BioTrack allows users to aggregate data from multiple sources, automatically annotate and rank abstracts based on preferences, and enable sharing of insights with a team. The summary highlights the most frequently mentioned biomarkers, technologies, applications, therapeutic areas, and companies across the abstracts.
This document discusses evaluating cancer testis antigens (CTAs) as targets for immunotherapy of triple negative breast cancer (TNBC). It finds that the gene expression of DKKL1, LDHC, MAGE-A3, PIWIL2, PLAC1, PRAME, PRSS50 and TSGA10 are moderately or highly expressed in human TNBC cell lines and datasets, making them potential immunotherapeutic targets. Real-time qRT-PCR and western blotting confirmed expression of some CTAs at the gene and protein level in the cell lines.
The expression of ITPK in normal colon and colorectal cancer cells - Postermaldjuan
This document summarizes a student's summer research project investigating expression levels of inositol trisphosphate kinase (ITPK) isoforms in normal colon cells and colorectal cancer cells. Preliminary studies found ITPKC overexpression inhibits cancer cell binding to liver cells, suggesting it is anti-metastatic. The student aimed to measure ITPK mRNA and protein levels to test if ITPKC is downregulated in cancer versus normal cells. Initial results showed ITPKA protein levels varied between cancer cell lines, and an additional higher molecular weight protein was lower in cancer cells. RNA extraction was initially unsuccessful but a second attempt yielded intact RNA for further analysis.
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoMauricio Lema
Ponencia en el VII Congreso internacional de coloproctología, Bogotá, 18.08.2016. Con énfasis en los estudios recientes en terapia antiangiogénica, y el impacto del lado del primario en el pronóstico (y aspectos predictivos) de la enfermedad metastásica.
This document discusses how tissue biomarker data can help tailor treatment pathways for colorectal cancer. It defines biomarkers and describes different types including diagnostic, prognostic, predictive, and surveillance. It outlines several molecular markers analyzed in CRC like extended RAS testing, BRAF mutations, microsatellite instability, tumor location, circulating tumor DNA, HER2 amplification, fusions, consensus molecular subtypes, and circulating tumor DNA for minimal residual disease. Several molecular markers are associated with prognosis and predictive of treatment response including anti-EGFR therapies. Analyzing these tissue and blood-based biomarkers is important for precision oncology in colorectal cancer.
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
ESPP presentation to EU Waste Water Network, 4th June 2024 “EU policies driving nutrient removal and recycling
and the revised UWWTD (Urban Waste Water Treatment Directive)”
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
3. KIRP
LGG
KIRC
LIHC
PAAD
ACC
MESO
LUAD
BRCA
GBM
SARC
STAD
HNSC
LAML
ESCA
OV
BLCA
LUSC
CESC
Proliferative Index (Counts/Million)
0 20 40 60 80 100 0 20 40 60 80
Breast
Lung
Pancreas
Esophagus
Stomach
Liver
Kidney (KIRC)
Bladder
Cervix
Kidney (KIRP)
Tumor Adjacent Normal Healthy (GTEx)
A B
Proliferative Index (Counts/Million)
Basal-like Her-2 Enriched Luminal A Luminal B Normal-like
rho=-0.65
Basal−like Luminal A Normal−like
10
20
30
40
50
60
ProliferativeIndex
Her2-Enriched Luminal B
0.8
ber
C D
E F
−100 −50 0 50
−100050100−50
PC1 (9.25%)
PC2(6.72%)
5
4
3
2
1
(A) Tumor proliferative index
(PI) distributions across
The Cancer Genome Atlas
(TCGA) cancers.
(B) PI values in healthy
G e n o t y p e - T i s s u e
E x p r e s s i o n ( G T E x )
samples (blue), TCGA
tumor-adjacent normal
tissue (red) and TCGA
tumor tissue (green).
(C) Heatmap of principal
c o m p o n e n t - t u m o r P I
c o r r e l a t i o n s a c r o s s
cancers.
Counts/Million)
60 80 100 0 20 40 60 80
Proliferative Index (Counts/Million)
Basal-like Her-2 Enriched Luminal A Luminal B Normal-like
rho=-0.65
al A Normal−likeLuminal B
AC
C
0.00.20.40.60.8
PrincipalComponentNumber
SpearmanCorrelation(rho)
BLCABRCACESCESCAG
BMHNSCKIRCKIRPLAM
LLG
G
LIHCLUADLUSCM
ESOO
V
PAADSARCSTAD
D
F
−100 −50 0 50
−100050100−50
PC1 (9.25%)
PC2(6.72%)
0 50
1 25
24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1C
7. small molecule
metabolic process
cellular
response to
camptothecin
cellular
localization
free ubiquitin chain
polymerization
coenzyme
metabolic
process
cofactor
metabolic
process
metabolic
process
primary
metabolic
process
antigen processing and
presentation of peptide
or polysaccharide
antigen via MHC class II
cell cycle
process
cell
proliferation
cellular
component
organization
or biogenesis
cellular
process
cellular
response
to DNA
damage
stimulus
chromosome
localization
chromosome
organization
chromosome
segregation
DNA
replication
microtubule−based
process
nitrogen
compound
metabolism
organic
substance
metabolism
regulation
of
cell
division
reproductive
process
single
organism
reproductive
process
single−organism
process
ACC
DNA
cytosine
deamination
lipoprotein
metabolism
negative
regulation
of
transposition
BLCA BRCA
anatomical
structure
formation
involved in
morphogenesis
angiogenesis
cell
morphogenesis
involved
in
differentiation
ovulation
positive regulation
of monocyte
chemotactic
protein−1 production
primary
follicle
stage
substrate−dependent
cerebral
cortex
tangential
migration
positive
regulation
of cell
adhesion
chromatin
assembly
extracellular
matrix
organization
regulation
of tight
junction
assembly
immune
response
inflammatory
response
leukocyte
migration
lipopolysaccharide−mediated
signaling
pathway
positive
regulation of
antigen
receptor−mediated
signaling pathway
regulation of
vascular
endothelial growth
factor receptor
signaling pathway
response
to
oxygen
levels
response
to
oxygen−containing
compound
response
to
stress
taxis
cellular
protein
metabolic
process
DNA
cytosine
deamination
macromolecule
modification
peptidyl−proline
hydroxylation
protein
hydroxylation
oxidation−reduction
process
acetyl−CoA
metabolism
angiogenesis
biological
adhesion
cell
activation
cell
adhesion
cellular
component
movement
extracellular
matrix
organization
immune
response
immune
system
process
nitrogen
cycle
metabolism
positive
regulation
of
vitamin D
biosynthesis
protein
hydroxylation
single−organism
metabolism
single−organism
process
CESC
dendritic
spine
maintenance
inorganic
cation
import
into
cell
protein initiator
methionine removal
regulation of
lateral mesodermal
cell fate
specification
response
to
ketone
GBM
histone
H3−K79
methylation
immune
system
process
multi−organism
metabolism
regulation
of leukocyte
cell−cell
adhesion
HNSC
amino−acid
betaine
metabolism
antigen processing and
presentation of peptide
or polysaccharide
antigen via MHC class II
cell
division cellular
component
organization
or
biogenesis
cellular
process
cellular
response
to DNA
damage
stimulus
microtubule−based
process
mitotic
cell
cycle
process
nuclear
division
protein
localization
to chromosome,
centromeric
region
protein
ubiquitination
regulation of
chromosome
segregation
single−organism
process
KIRC
catabolic
process
peptidyl−proline
hydroxylation
anatomical
structure
development
cell
cycle
process
cell
proliferation
cellular
component
movement
cellular
component
organization
or biogenesis
cellular
process
cellular
response to
DNA damage
stimulus
chromosome
segregation
collagen
metabolism
developmental
process
establishment
of chromosome
localization
macromolecule
metabolism
microtubule−based
process
organelle
fission
protein
hydroxylation
regulation
of
cell
division
reproductive
process
single
organism
reproductive
process
single−organism
process
KIRP
arachidonic
acid
metabolic
process
fatty−acyl−CoA
catabolic
process
positive
regulation
of lipid
metabolic
process
protein
polyubiquitination
sterol
metabolic
process
antigen
processing
and
presentation
biological
regulation
cell
cycle
detection of
chemical stimulus
involved in
sensory perception
of taste
fatty
acid
derivative
metabolism
immune
system
process
mesoderm
development
negative
regulation of
leukocyte
proliferation
sterol
metabolism
LAML
macromolecule
metabolic
process
calcium ion
transmembrane import
into mitochondrion
anterior/posterior
pattern
specification
cell
cycle
process
cellular
component
organization
or biogenesis
cellular
process
chromosome
organization
chromosome
segregation
developmental
process
dimethylallyl
diphosphate
biosynthesis
microtubule−based
process
negative
regulation
of viral
process
single−organism
cellular
localization
single−organism
process
LGG
protein
stabilization
regulation of
establishment of
protein localization
to chromosome
connective
tissue
development
extracellular
matrix
disassembly
L−ornithine
transmembrane
transport
protein
stabilization
pyruvate
metabolism
response
to
oxidative
stress
spermine
metabolism
LIHC
cell
cycle
single−organism
cellular
processanaphase−promoting complex−dependent proteasomal
ubiquitin−dependent protein catabolic process
nicotinamide
nucleotide
metabolic
process
nucleotide
phosphorylation
spermine
metabolic
process
antigen
processing
and
presentation
binding
of sperm
to zona
pellucida
cell
division
cell
proliferation
cellular
component
organization
or
biogenesis
cellular
process
coenzyme
A
transmembrane
transport
heterotypic
cell−cell
adhesion
intermediate
filament−based
process
microtubule−based
process
mitotic
cell
cycle
process
nuclear
division
regulation of
chromosome
segregation
response
to
inorganic
substance
single−organism
carbohydrate
catabolism
single−organism
process
LUAD
glycerolipid
catabolic
process
epithelial
fluid transport
lipid
transport
anatomical
structure
development
extracellular matrix
organization
immune
system
process
negative
regulation of
endothelial
cell apoptotic
process
platelet
degranulationprotein
activation
cascade
response
to
stimulus
single−multicellular
organism
process
LUSC
alpha−amino
acid
metabolic
process
DNA
metabolic
process
DNA
replication
ethanol
oxidation
negative
regulation
of
biological
process
negative
regulation of
cellular process
protein
K6−linked
ubiquitination
purine nucleoside
bisphosphate
catabolic process
pyrimidine
deoxyribonucleoside
metabolic
process
regulation
of molecular
function
regulation of
phosphorus
metabolic process
signal
transduction
in response
to DNA
damage
regulation
of smooth
muscle
cell
migration
cellular response
to radiation
actin
filament−based
process
angiogenesis
cell
cycle
process
cell
proliferation
cellular
component
movement
cellular
component
organization
or
biogenesis
chromosome
organization
chromosome
segregation
DNA
replication
establishment
of
chromosome
localization
microtubule−based
process
regulation of
chromosome
segregation
single−organism
process
wound
healing
MESO
amino sugar
metabolism
binding of
sperm to zona
pellucida
cell
communication
membrane
biogenesis
positive
regulation of
glucose transport
response to
insulin−like
growth factor
stimulus
signaling
single
organism
signaling
telencephalon
regionalization
OV
actin
filament−based
process
antigen
processing and
presentation of
exogenous
peptide antigen
biological
regulation
cell
cycle
process
cell differentiation
involved in embryonic
placenta development
cell
proliferation
cell−substrate
adhesion
cellular
component
movement
cellular component
organization or
biogenesis
chromosome
segregation
DNA
replication
microtubule−based
process
nuclear
division
organelle
localization
regulation of
chromosome
segregation response to
organic cyclic
compound
viral
process
PAAD
cell
differentiation
trigeminal
ganglion
development
cellular aromatic
compound metabolic
process
heterocycle
metabolic
process
immune
response
response to
cytokine
metabolic
process
biological_process
immune
system
process
multi−organism
process
negative
regulation
of
multi−organism
process nitrogen
compound
metabolism
nuclear
inner
membrane
organization
organic
cyclic
compound
metabolism
organic
substance
metabolism
single−organism
process
SARC
cellular
response
to
light
stimulus
negative regulation
of retinoic acid
receptor signaling
pathway
positive regulation of
translational
initiation in response
to starvation
negative
regulation
of RNA
export from
nucleus
sodium−independent
organic
anion
transportdetection of
chemical stimulus
involved in sensory
perception of smell multicellular
organismal
process
response
to
stimulus
sodium−independent
organic
anion
transport
STAD
catabolic
process
cobalt ion
transport
mRNA
metabolic
process
ncRNA
metabolic
process
metabolic
process
primary
metabolic
process
peptide
biosynthetic
process
snRNA
transcription
from RNA
polymerase
II promoter
antigen
receptor−mediated
signaling pathway
cell
cycle
cellular
component
organization
or biogenesis
cellular
metabolism
cellular
process
epithelium
migration
immune
system
process
interspecies
interaction
between
organisms
intracellular
transport
localization
macromolecule
catabolism
macromolecule
metabolism
nitrogen
compound
metabolism
organic
substance
metabolism
snRNA
transcription
Proliferation
Informative
Non-proliferation
Informative
angiotensin
maturation
demethylation
methylation
ESCA
Cell Proliferation/Divison
Associated Process
Gene ontology enrichment analysis on survival-associated genes in each cancer.
Adrenocortical Carcinoma Kidney Renal Clear Cell Carcinoma Kidney Renal Papillary Cell Carcinoma Pancreatic Adenocarcinoma
Brain Lower Grade Glioma Lung Adenocarcinoma Mesothelioma
Bladder Urothelial Carcnioma Breast Invasive Carcinoma
Cervical Squamous Cell &
Endocervical Adenocarcinoma Ovarian Serous Cystadenocarcinoma
Glioblastoma multiforme Head and Neck Squamous Cell Carcinoma Acute Myeloid Leukemia Sarcoma
Liver Hepatocellular Carcinoma Lung Squamous Cell Carcinoma Stomach Adenocarcinoma Esophageal Carcinoma
Proliferative
-Informative
Cancers
Non-
Proliferative
Informative
Cancers
9. Full Patient Cohort (n=6,312)
Shortest Survivors
(n=342)
Longest Survivors
(n=342)
Training Cohort
(n=479)
Testing Cohort
(n=205)
Dichotomize 18 shortest
and 18 longest surviving
patients for each cancer
Randomly split into
training (70%) and
testing cohorts (30%)
Feature selection in
training cohort
Model evaluation in
Testing Cohort
AUC
Frequency
0.5 0.6 0.7 0.8 0.9
0
2
4
6
8
10
12
Observed PIC AUC
1 2 3 4 5
0.5
Number of PICs in Permutation
AUC
A
DC
12
0.6
0.7
0.8
rho=0.569
False positive rateTruepositiverate
0.0 0.2 0.4 0.6 0.8 1.0
0.00.20.40.60.81.0
All Cancers (AUC:0.651)
PICs (AUC:0.856)
Non PICs (AUC: 0.634
All Cancers (AUC: 0.651)
PICs (AUC: 0.856)
Non PICs (AUC: 0.634)
B
(A) Workflow for cross-
cancer survival model
generation.
(B) Receiver operating
characteristic (ROC)
curve for multivariate
Cox regression with
LASSO for variable
selection on all 19
cancers (blue), PICs
only (green) and non-
PICs only (orange).
(C) Histogram showing
the distribution of
ROC area under the
curve (AUC) values
for survival models
generated on 100
randomly sampled
s e t s o f c a n c e r s
equivalent in number
to the PICs.
(D) The ROC curve AUC
values are directly
proportional to the
n u m b e r o f P I C s
included in random
sample sets
11. 2 3 4 5 6
10
20
30
40
50
60
Log10 Somatic Mutation Number
ProliferativeIndex Basal-like
Her2-Enriched
Luminal A
Luminal B
Normal-like
Unknown
0
20
40
60
80
ProliferativeIndex
RELN Mutant
RELN Wild Type
All Tumors Basal-Like HER2-Enriched Luminal A Luminal B
0 1000 3000 5000
0.00.40.8
PercentSurvival
Days
RELN Low Expresser or PAM
RELN High Expresser
A
C D
p=0.08
2000 4000 6000
0 1 2 3 4 5 6 7
0
1
2
3
4
5
6
7
Expected P−value (−log10 scale)
ObservedP−value(−log10scale)
TP53
RB1
PIK3CA
B
(A) Tumor proliferative index (PI) is correlated with TCGA breast cancer somatic mutation burden. (B) Q-Q plot of p-
values derived from gene mutation burden-PI associations. (C) TCGA breast tumors containing non-synonymous
mutations in RELN have higher PI compared to wild-type. (D) Kaplan-Meier survival plot shows reduced expression or
protein-altering mutations in RELN are markers of poor prognosis in patients with basal breast cancer.