1. Kras and BRAF mutations are important for determining treatment with cetuximab and differentiating Lynch syndrome from sporadic colorectal cancers with microsatellite instability.
2. CpG island methylation phenotype (CIMP) refers to gene silencing through methylation of CpG islands.
3. Rare epimutations can cause multiple cancers through methylation-induced silencing of genes like MLH1.
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.
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.
Present and Future Impact of Cytogenetics on Acute Myeloid Leukemialarriva
Cytogenetics is an advancement in which clinicians can look for specific genetic mutations of chromosomal DNA and use that information to determine patient prognosis and individualize therapy. In this presentation I cover what cytogenetics are, how they impact patient risk, what therapies to use based on risk, and how genetically targeted agents may be used in the future.
Microsatellite instability testing is an important part in diagnostics in Metastatic cancer settings after the FDA has given approval for tissue agnostic indications in almost all solid cancers. MSI by PCR and MMR status by IHC is also helpful for evaluation of genetic risk in Colon and Endometrial cancers
Present and Future Impact of Cytogenetics on Acute Myeloid Leukemialarriva
Cytogenetics is an advancement in which clinicians can look for specific genetic mutations of chromosomal DNA and use that information to determine patient prognosis and individualize therapy. In this presentation I cover what cytogenetics are, how they impact patient risk, what therapies to use based on risk, and how genetically targeted agents may be used in the future.
Microsatellite instability testing is an important part in diagnostics in Metastatic cancer settings after the FDA has given approval for tissue agnostic indications in almost all solid cancers. MSI by PCR and MMR status by IHC is also helpful for evaluation of genetic risk in Colon and Endometrial cancers
NSCLC: diagnóstico molecular, pronóstico y seguimiento; CTCMauricio Lema
Lo nuevo en diagnóstico molecular, pronóstico y seguimiento en NSCLC, y el impacto pronóstico de las Células Tumorales Circulantes. Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las la presentación de lo nuevo en terapia sistémica en NSCLC).
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
Advanced prostate cancer is highly heterogeneous but this inter-patient heterogeneity has until recently not been understood. We have through an international research effort dissected the molecular landscape of advanced castration resistant prostate, elucidating key molecular targets in this group of diseases. We have also shown that PARP inhibitors have antitumor activity against a significant proportion of these cancers, mainly in men whose cancers harbor DNA repair defects.
• Gastric cancer prognosis and cell ratio factors Oleg Kshivets
OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting gastric cancer (EC) patients GCP) survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations.
METHODS: We analyzed data of 799 consecutive GCP (T1-4N0-2M0) (age=57.1±9.4 years; tumor size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2022 (m=558, f=241; total gastrectomies=173, distal gastrectomies=461; proximal gastrectomies=165; combined gastrectomies=247 with resection of esophagus, pancreas, liver, duodenum, diaphragm, colon transversum, splenectomy, etc; only surgery-S=624, adjuvant chemoimmunotherapy-AT=175 (5-FU + thymalin/taktivin); T1=238, T2=220, T3=184, T4=157; N0=437, N1=109, N2=253, M0=799; G1=222, G2=164, G3=413. Variables selected for prognosis study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of GCP were evaluated using a log-rank test. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 2128.9±2300.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 51.9%, 20 years – 39%, 30 years – 27.2%. 318 GCP lived more than 5 years (LS=4304.5±2290.6 days), 169 GCP – more than 10 years (LS=5919.5±2020 days). 290 GCP died because of GC (LS=651±347.2 days). Cox modeling displayed that G CP survival significantly depended on CRF: healthy cells/CC, erythrocytes/CC, monocytes/CC, phase transition (PT) in terms of synergetics early—invasive cancer; PT N0--N12, age, G1-3, hemorrhage time, ESS, sex, AT, prothrombin index, residual nitrogen. Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early—invasive cancer (rank=1); PT N0--N12 (2); healthy cells/CC (3), erythrocytes/CC (4), thrombocytes/CC (5), monocytes/CC (6), segmented neutrophils/CC (7), leucocytes/CC (8), lymphocytes/CC (9), stick neutrophils/CC (10), eosinophils/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: GCP survival after radical procedures significantly depended on CRF.
Never-smoker with Lung cancer in Southern California. Never-smokers with lung cancer have distinct genetic changes. Chao Family Comprehensive Cancer Center at UCI Irvine offers cutting edge clinical trials. Please call 1-714-456-8000
Alphabet Soup - Biomarker testing for colon and rectal cancer patients - KRAS...Fight Colorectal Cancer
Dr. Cathy Eng's presentation regarding biomarkers. Explaining why colon and rectal cancer patients should undergo testing for KRAS, NRAS and other tumor tests.
Essentials of Automations: The Art of Triggers and Actions in FMESafe Software
In this second installment of our Essentials of Automations webinar series, we’ll explore the landscape of triggers and actions, guiding you through the nuances of authoring and adapting workspaces for seamless automations. Gain an understanding of the full spectrum of triggers and actions available in FME, empowering you to enhance your workspaces for efficient automation.
We’ll kick things off by showcasing the most commonly used event-based triggers, introducing you to various automation workflows like manual triggers, schedules, directory watchers, and more. Plus, see how these elements play out in real scenarios.
Whether you’re tweaking your current setup or building from the ground up, this session will arm you with the tools and insights needed to transform your FME usage into a powerhouse of productivity. Join us to discover effective strategies that simplify complex processes, enhancing your productivity and transforming your data management practices with FME. Let’s turn complexity into clarity and make your workspaces work wonders!
Unlocking Productivity: Leveraging the Potential of Copilot in Microsoft 365, a presentation by Christoforos Vlachos, Senior Solutions Manager – Modern Workplace, Uni Systems
Sudheer Mechineni, Head of Application Frameworks, Standard Chartered Bank
Discover how Standard Chartered Bank harnessed the power of Neo4j to transform complex data access challenges into a dynamic, scalable graph database solution. This keynote will cover their journey from initial adoption to deploying a fully automated, enterprise-grade causal cluster, highlighting key strategies for modelling organisational changes and ensuring robust disaster recovery. Learn how these innovations have not only enhanced Standard Chartered Bank’s data infrastructure but also positioned them as pioneers in the banking sector’s adoption of graph technology.
Removing Uninteresting Bytes in Software FuzzingAftab Hussain
Imagine a world where software fuzzing, the process of mutating bytes in test seeds to uncover hidden and erroneous program behaviors, becomes faster and more effective. A lot depends on the initial seeds, which can significantly dictate the trajectory of a fuzzing campaign, particularly in terms of how long it takes to uncover interesting behaviour in your code. We introduce DIAR, a technique designed to speedup fuzzing campaigns by pinpointing and eliminating those uninteresting bytes in the seeds. Picture this: instead of wasting valuable resources on meaningless mutations in large, bloated seeds, DIAR removes the unnecessary bytes, streamlining the entire process.
In this work, we equipped AFL, a popular fuzzer, with DIAR and examined two critical Linux libraries -- Libxml's xmllint, a tool for parsing xml documents, and Binutil's readelf, an essential debugging and security analysis command-line tool used to display detailed information about ELF (Executable and Linkable Format). Our preliminary results show that AFL+DIAR does not only discover new paths more quickly but also achieves higher coverage overall. This work thus showcases how starting with lean and optimized seeds can lead to faster, more comprehensive fuzzing campaigns -- and DIAR helps you find such seeds.
- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
Sectoral targets and attacks as well as the cost of ransom
Global APT activity, AI usage, actor and tactic profiles, and implications
Rise in volumes of AI-powered cyberattacks
Major cyber events in 2024
Malware and malicious payload trends
Cyberattack types and targets
Vulnerability exploit attempts on CVEs
Attacks on counties – USA
Expansion of bot farms – how, where, and why
In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
Why are attacks on smart factories rising?
Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
In his public lecture, Christian Timmerer provides insights into the fascinating history of video streaming, starting from its humble beginnings before YouTube to the groundbreaking technologies that now dominate platforms like Netflix and ORF ON. Timmerer also presents provocative contributions of his own that have significantly influenced the industry. He concludes by looking at future challenges and invites the audience to join in a discussion.
PHP Frameworks: I want to break free (IPC Berlin 2024)Ralf Eggert
In this presentation, we examine the challenges and limitations of relying too heavily on PHP frameworks in web development. We discuss the history of PHP and its frameworks to understand how this dependence has evolved. The focus will be on providing concrete tips and strategies to reduce reliance on these frameworks, based on real-world examples and practical considerations. The goal is to equip developers with the skills and knowledge to create more flexible and future-proof web applications. We'll explore the importance of maintaining autonomy in a rapidly changing tech landscape and how to make informed decisions in PHP development.
This talk is aimed at encouraging a more independent approach to using PHP frameworks, moving towards a more flexible and future-proof approach to PHP development.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
Pushing the limits of ePRTC: 100ns holdover for 100 daysAdtran
At WSTS 2024, Alon Stern explored the topic of parametric holdover and explained how recent research findings can be implemented in real-world PNT networks to achieve 100 nanoseconds of accuracy for up to 100 days.
GraphSummit Singapore | The Future of Agility: Supercharging Digital Transfor...Neo4j
Leonard Jayamohan, Partner & Generative AI Lead, Deloitte
This keynote will reveal how Deloitte leverages Neo4j’s graph power for groundbreaking digital twin solutions, achieving a staggering 100x performance boost. Discover the essential role knowledge graphs play in successful generative AI implementations. Plus, get an exclusive look at an innovative Neo4j + Generative AI solution Deloitte is developing in-house.
UiPath Test Automation using UiPath Test Suite series, part 5DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 5. In this session, we will cover CI/CD with devops.
Topics covered:
CI/CD with in UiPath
End-to-end overview of CI/CD pipeline with Azure devops
Speaker:
Lyndsey Byblow, Test Suite Sales Engineer @ UiPath, Inc.
Dr. Sean Tan, Head of Data Science, Changi Airport Group
Discover how Changi Airport Group (CAG) leverages graph technologies and generative AI to revolutionize their search capabilities. This session delves into the unique search needs of CAG’s diverse passengers and customers, showcasing how graph data structures enhance the accuracy and relevance of AI-generated search results, mitigating the risk of “hallucinations” and improving the overall customer journey.
SAP Sapphire 2024 - ASUG301 building better apps with SAP Fiori.pdfPeter Spielvogel
Building better applications for business users with SAP Fiori.
• What is SAP Fiori and why it matters to you
• How a better user experience drives measurable business benefits
• How to get started with SAP Fiori today
• How SAP Fiori elements accelerates application development
• How SAP Build Code includes SAP Fiori tools and other generative artificial intelligence capabilities
• How SAP Fiori paves the way for using AI in SAP apps
GraphSummit Singapore | The Art of the Possible with Graph - Q2 2024Neo4j
Neha Bajwa, Vice President of Product Marketing, Neo4j
Join us as we explore breakthrough innovations enabled by interconnected data and AI. Discover firsthand how organizations use relationships in data to uncover contextual insights and solve our most pressing challenges – from optimizing supply chains, detecting fraud, and improving customer experiences to accelerating drug discoveries.
LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...
MCC 2011 - Slide 6
1. ESO-ESSO Masterclass in colorectal cancer surgery Genetic and epigenetic analysis of sporadic colon cancer-Decision & treatment Professor Sir John Burn MD FRCP FRCPCH FRCOG FMedSci Institute of Human Genetics, Newcastle University, UK Institute of Human Genetics Newcastle University Centre for Life, Newcastle UK
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3. December 11 th 2008;359:2567-2578 CAPP2: 1009 Lynch syndrome recruits Gail Barker Anne-Marie Gerdes Julie Coaker Lynn Reed John Mathers Tim Bishop 600mg aspirin for up to 4 yrs had no effect
4. CAPP2: Per protocol analysis (primary endpoint CRC after 2 years treatment) significantly fewer colorectal cancers [submitted] HR 0.45 (0.22-0.93) p = 0.03 IRR 0.41 (0.20-0.84) p= 0.01
5. CAPP2 per protocol analysis All Lynch syndrome cancers HR 0.48 (0.28-0.83)p= 0.008 IRR 0.44 (0.26-0.75)p=0.002
7. Normal epithelium Adenoma Carcinoma Metastases APC, K-ras 12p, DCC 18q, p53 17p, …….. 85 % 15 % CIN MSI FAP HNPCC hMLH1, hMSH2, TGF-ß RII, Bax, TCF4, ACVRII, Caspase 5 ………. The Genomic Pathogenesis of Colorectal Cancer
8. Molecular Classification of Colorectal Cancer Jass, Histopathology 2007, 50, 113–130 FAP Less responsive To 5FU? Gallinger group Ribic CM et al NEJM 2003 ;349:247-57,
9. Colorectal Cancer Genetics & 5-FU Ribic CM NEJM 2003 MSS MSI Hazard Ratio 0.69 (0.50-0.94) p=0.02 2.17 (0.84-5.55) p=0.10 Courtesy Steve Gallinger
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12. SEQUENOM TM MALDI TOF MASS SPECTROMETER Matrix Assisted Laser Desorption/Ionisation Time of Flight mass spectrometry Laser Flight path Detector Time of flight Sequenom chip
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14. T G G A C C G T T C A A C - ve - ve - ve - ve - ve - ve - ve Polymerase - ve - ve - ve - ve - ve - ve - ve C
18. Cytosine methylation at CpG islands CpG m CpG N N HO NH 2 1 2 3 4 5 6 CH 3 5-methylcytosine cytosine Normal biallelic expression Biallelic methylation – eg cancer cells N N HO NH 2 1 2 3 4 5 6 TF TF
19. A C A T C A C G T G A TT A C A Sodium bisulphite (NaHS0 3) conversion of genomic DNA Genomic DNA Treatment with sodium bisulphite Unmethylated sequence Methylated sequence A T A T T A C G T G A TT A T A A T A T T A T G T G A TT A T A
25. ELISA reactivity reveals immune response to Neopeptides in Lynch syndrome patients with Previous cancer and in MMR mutation carriers patients healthy controls mutation carriers
27. T-cells infiltrating MSI-H CRC recognize MSI-induced FSP Exemplary results derived from a MSI-H CRC-patient Schwitalle et al. Gastroenterology 2008
28. Truncating mutations in ß2m are more common with tumour progression but absent from mets Kloor et al Int J Cancer 2007 UICC IV, M1: No truncating mutation in CRC with metastasis ß2m mutation frequency is signif. lower in M1 vs M0 MSI CRC ?Intact ß2m needed for metastasis formation in MSI-H CRC UICC III 9/22 (40.9%) UICC IV 2/26 (7.7%) p=0.01 Only silent mutations or single AA exchanges, w/o functional loss of ß2m
December 11 th Gail, our manager, was retiring and our statistician had gone on maternity leave All the money was gone but Anne Marie had come as a visiting fellow so I asked her to plot out the cancers covering the whole period as we now had data up to 10 years since commencement. I jokingly predicted that the lines would separate at 4 yeasr just after our last analysis
Per protocol analysis showing proportion who developed CRC We decided to use tablet counts. 2 per day for 2 years equals 1460 tabs We rounded down to 1400 (blind to the data) to allow for those who missed some tablets Note there are few cases at 10 years out so confidence limits expand Note also that the aspirin placebo group who dropped out early are the same as the aspirin treated groups suggesting they may have dropped into self medication IRR is equivalent to HR using Poisson to allow for multiple primary events eg a person gets endometrial cancer at 3 years and crc at 6 years
THIS GRAPH ANALYSES ALL Lynch syndrome cancers rather than just colorectal Note again that the early finish placebo aspirin group are tracking with the main treatment line.
Mismatch repair – corrects bases which are not paired according to the Watson-Crick base pairing A-T and C-G.
CIMP-negative, chromosomal instability, mainly MSS, origin in adenomas (may be sporadic, FAP-associated or MUTYH (formerly MYH) polyposis associated 108) (57%). CIMP-low, KRAS mutation, MGMT methylation, chromosomal instability, MSS or MSI-L, origin in adenomas or serrated polyps (20%). CIMP-high, methylation of MLH1, BRAF mutation, chromosomally stable, MSI-H, origin in serrated polyps, known generally as sporadic MSI-H (12%). CIMP-high, partial methylation of MLH1, BRAF mutation, chromosomally stable, MSS or MSI-L, origin in serrated polyps (8%). Lynch syndrome, CIMP-negative, BRAF mutation negative, chromosomally stable, MSI-H, origin in adenomas (3%) (familial MSI-H CRC) .
Mismatch repair – corrects bases which are not paired according to the Watson-Crick base pairing A-T and C-G.
The first case of what we now term a constitutional epimutation to be identified in humans was reported by Richard Kolodner’s group in 2002 in the mismatch repair gene, MLH1, in a patient diagnosed with Lynch syndrome. Constitutional epimutations of MLH1 are characterised by soma-wide monoallelic methylation of the MLH1 promoter, that is methylation of a single allele. We know this because some epimutation carriers are heterozygous for the common G/A SNP in the MLH1 promoter, and through methylation-sequencing of individual alleles, the methylation is shown to be associated with just one genetic allele. Because this methylation is present in normal somatic tissues, epimutation carriers are typically identified by the detection of methylation in their peripheral blood DNA. The effect of the epimutation is to cause transcriptional silencing of the methylated allele, and once again we know this by tracing the activity of SNPs that are present within the expressed part of the gene. In cases that are heterozygous for an exonic SNP, analysis of their RNA has shown that only one allele is detected in their mRNA, due to loss of transcriptional activity from the other allele. Finally, MLH1 epimutations occur in the context of a normal gene sequence – there are no genetic mutations identified in the gene or its vicinity.
Patient YT, represents the youngest affected case reported to date, but his profile is otherwise typical of other cases with a constitutional MLH1 epimutation. YT was 18 years old when he presented with cancer of the ascending colon, but had no family history of LS. The tumour demonstrated microsatellite instability and immunohistochemical loss of MLH1 and PMS2, but no germline mutation was identified within MLH1 and no evidence for structural alterations of MLH1 or MSH2 was identified by MLPA. Methylation testing revealed hemiallelic soma-wide methylation of the MLH1 promoter, as shown in these epigrams. Approximately half of his alleles were hypermethylated, as seen by the black dots, whilst the other half were unmethylated as indicated by the white dots.
A small number of families in whom the affected members have loss of the MSH2 protein in their tumours, have now been identified with deletions of the EPCAM gene located immediately upstream of MLH1, which give rise to a somatic epimutation of MSH2. In these cases, there is mosaic methylation of the MSH2 promoter, which is predominant in epithelial tissues. Although MSH2 itself in intact, this epigenetic error is caused by a linked deletion of the final exons of EPCAM. These abolish the transcription termination signal and cause elongation of transcription into MSH2 to produce fusion transcripts, ultimately leading to MSH2 methylation. Since this type of epimutation is associated with a cis-acting genetic defect, it demonstrates dominant inheritance, and has been found in large Lynch syndrome kindreds.