SlideShare a Scribd company logo
1 of 43
Cancer Genetics


     Judy E. Garber, MD MPH
Director, Cancer Genetics and Prevention
      Dana-Farber Cancer Institute
An Overview of Cancer Genetics
Cancer is a Genetic Disease
Normal cells and Cancer cells contain the same 30,000 genes
        what distinguishes them is which of the genes
                    are turned on and off




           Normal                           Cancer



        Which genes are activated in cancer?
Chromosomes, DNA, and Genes
                                                     Gene
           Nucleus
    Cell              Chromosomes




                                                            Protein

Adapted from Understanding Gene Testing, NIH, 1995
The DNA Double Helix
  Sugar
phosphate                                      Base pair
backbone                Bases




               Adenine (A)      Cytosine (C)
               Thymine (T)      Guanine (G)
Normal Male Karyotype


                     p
                     Centromere


                     q




                Chromosome 5
Genetic Code

             A codon is made of 3 base pairs
                    64 codons total

1 codon (AUG) encodes         61 codons encode   3 codons stop
  methionine and starts        20 amino acids        protein
translation of all proteins   (redundant code)     translation

        A    U    G              G    C    A     U   A   A

            Met                      Ala
Disease-Associated Mutations
       Alter Protein Function




  Functional protein   Nonfunctional or
                       missing protein
Autosomal Dominant Inheritance

   Each child has 50%
    chance of inheriting the
    mutation
   No “skipped generations”
   Equally transmitted by
    men and women

                               Unaffected
                               Affected
The Two-Hit Hypothesis


First hit




    First hit in
                          Second hit
    germline
                           (tumor)
Tumor Suppressor Genes


     Normal genes
    (prevent cancer)


       1st mutation
   (susceptible carrier)


   2nd mutation or loss
    (leads to cancer)
Oncogenes

                Normal genes
                (regulate cell
                   growth)

                 1st mutation
                   (leads to
                accelerated cell
                   division)

1 mutation sufficient for role in cancer development
Normal (male) chromosomes and
BRCA1-deficient cancer cells with
gross chromosomal abnormalities
An Overview of Cancer Genetics
More Subtle Pedigrees




PR 60                            CO 61?



                             55* OV 59



        BR 32        BR 34

                               *TAH/BSO at 40
Genetic Testing 2012
• Genetic testing requires a DNA sample from
  blood, saliva or other tissue
• Testing costs are usually covered by health
  insurance, at least partially
• Laws to prevent discrimination in health
  insurance exist (GINA)
• Testing is often offered at the time of cancer
  diagnosis, because the information can affect
  management decisions
• Autonomy and Access are still important
+
Once the mutation is
found in one person
in the family after full
price testing, the rest
of the family can be
tested to see whether
they do or do NOT
share the mutation.
The “single site”
testing is usually
about $500.
BR/OV Cancer Risk Management
    Options for BRCA Mutation Carriers
Surveillance (does not  risk)
• Mammogram, MRI, Exam, +/- US
• (TransVaginal Ultrasound, CA125)
Chemoprevention
• Tamoxifen/ Raloxifene?
   Exemestane? Other?
• Birth Control Pills  Ov ca risk
Prophylactic Surgery
• 90% Bilateral mastectomy
• Removal ovaries & fallopian tubes:
   90% Ov ca risk; if done
   premenopausal, ~50%  BrCa risk
I’M OUT OF
ESTROGEN
AND I AM
NOT HAPPY
ABOUT IT
Risk of Colorectal Cancer (CRC)

General population         5%

 Personal history of
colorectal neoplasia             15%–20%

      Inflammatory                        15%–40%
     bowel disease

  HNPCC mutation                                           70%–80%


               FAP                                              >95%

                       0    20       40      60       80      100
                                  Lifetime risk (%)
Hereditary Non-Polyposis Colorectal
Cancer (HNPCC, Lynch Syndrome)

                                • Colon, Uterine and
                                other cancers
                                • In HNPCC, the tumor
        CO 45           UT 38
                                tissue stored in a
                        CO 40   pathology department
         _      +               can be studied for
                                evidence that the
CO 28        Cecum 35           syndrome is present, so
ST 32
                                even a deceased relative
                                can be informative
                4
A Li - F raum eni S yndrom e K indred



                             C R C , 72               Lung, 48     80




                                                                        O S , 14
    Laryn x, 56                                      B reast, 26
                                                                        B reast, 22, 27
                                                     S T S , 33*
                                                                        S tom ach, 32



                                     B reast, 32   ACC, 5
                                                   O S , 14
                                                   S T S , 26*
* tum or in R T field of prior m alig na ncy
An Overview of Cancer Genetics
FDG-PET/CT Screening in LFS Results



                             Fused   PET/CT




                                       CT
Survival of TP53 Mutation Carriers in
Surveillance and Non-Surveillance Groups




                    Villani A et al. Lancet Oncol 2011;12:559-567
Decisions Potentially Influenced by
BRCA1/2 Status in Breast Cancer Patients

• Management of newly diagnosed patients
  – Primary Therapy: Surgical Options
  – Chemotherapy
  – Hormonal therapy
• Management of breast cancer survivors
  – Additional primary breast cancer risk
  – Ovarian cancer risk
  – Treatment of metastatic disease
• Implications for Relatives
Breast Cancer Subtypes are Associated
   with Different Germline Mutations

                         ER+ PR+/HER2-
                         BRCA2, TP53




                         ER+ or ER-/HER2+
                         TP53




                         ER-, PR-, HER2-
                         BRCA1
Kaplan-Meier estimates of recurrence-free survival
   and overall survival after neoadjuvant T-FAC by :



BRCA status




 Path CR




  TNBC



                          Arun B et al. J Clin Oncol 2011;29:3739-3746
-
Expanded Commercial Cancer Genetic
          Testing is Here
TP53 Germline
                              Deletion in Patient
                                 With t-AML




BR 37         +
OV 39
R-OV 42
AML 42

          3

                  Link DC et al. JAMA 2011;305:1568-1576
Pharmacogenetics:
Predicting Efficacy and Toxicity
=



Breast Cancer
A Paradigm Shift – The Genomic View of Cancer

From Anatomy…                                               From
                                     KIT                 Germline
                               (Imatinib)
    • Lung
                 Tumor                        Blood
                Genomic                      Genomic
    • Breast    Profiling          EGFR      Profiling
                               (Erlotinib)



    •Prostate                       HER2
                            (Trastuzumab)



    • Colon
                                  BRAF
                              (PLX4032)


    • Brain
                                 PIK3CA
                               (BEZ235)
Potential Findings from Sequencing DNA from Tumor
      & Blood of DFCI Cancer Patients in PCMP


• Tumor genome: treatment targets, predictors of response
• Personal genome:
   • Variation in drug metabolizing genes that affect dose or
     choice of agent
   • Mutations in genes that confer  risk of the patient’s
     cancer and related cancers (e.g, BRCA, HNPCC),
     important to patient and family
   • Mutations in genes associated with Non-Cancer
     conditions that could be more important to relatives
     (e.g., long QT; Fragile X)
An Overview of Cancer Genetics
An Overview of Cancer Genetics
Learn more about the
                                    DFCI Gene Display.


Gene Display in the Yawkey Center for Cancer Care
Audience Q&A


What about people who are adopted
     and don’t know anything
    about their family history?
Audience Q&A


What is does the insurance
   industry think about
 preventative surgeries?
Audience Q&A


   For insurance purposes,
 do you have to build a case
to justify preventative surgery
  based on genetic testing?
Resources and Additional Information


 • Check out the Cancer Genetics and Prevention Program
   at Dana-Farber.


 • Watch Dr. Judy Garber discuss her work as the director
   of Cancer Genetics and Prevention Program.


 • View more resources available through DFCI for patients
   and families dealing with cancer.


           To schedule an appointment at DFCI, click here.

More Related Content

What's hot

Chapter 1 cancer genome
Chapter 1 cancer genomeChapter 1 cancer genome
Chapter 1 cancer genomeNilesh Kucha
 
Cell biology and cancer
Cell biology and cancerCell biology and cancer
Cell biology and cancerKim B
 
Cancer and genetic influences
Cancer and genetic influences Cancer and genetic influences
Cancer and genetic influences Shalimar Shadeed
 
Molecular Genetics of Cancer
Molecular Genetics of CancerMolecular Genetics of Cancer
Molecular Genetics of CancerNeha Vats
 
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...QIAGEN
 
Hereditary Cancer Syndrome
Hereditary Cancer SyndromeHereditary Cancer Syndrome
Hereditary Cancer SyndromeSujoy Dasgupta
 
Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs
Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs
Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs Karobi Moitra CFD, MS, PhD
 
Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.Mohamed Abdulla
 
7.Cancer Genetics.Oct.09
7.Cancer Genetics.Oct.097.Cancer Genetics.Oct.09
7.Cancer Genetics.Oct.09ghalan
 
Oncogene and tumor suppressor gene
Oncogene and tumor suppressor geneOncogene and tumor suppressor gene
Oncogene and tumor suppressor geneAJEESH BL
 
Chapter 2 molecular methods in cancer
Chapter 2 molecular methods in cancerChapter 2 molecular methods in cancer
Chapter 2 molecular methods in cancerNilesh Kucha
 

What's hot (20)

Cancer genome
Cancer genomeCancer genome
Cancer genome
 
Cancer genetics
Cancer genetics Cancer genetics
Cancer genetics
 
Hallmarks of cancer
Hallmarks of cancerHallmarks of cancer
Hallmarks of cancer
 
Oncogenes
OncogenesOncogenes
Oncogenes
 
Oncogenes
Oncogenes Oncogenes
Oncogenes
 
Cancer epigenetics
Cancer epigenetics Cancer epigenetics
Cancer epigenetics
 
Chapter 1 cancer genome
Chapter 1 cancer genomeChapter 1 cancer genome
Chapter 1 cancer genome
 
Cell biology and cancer
Cell biology and cancerCell biology and cancer
Cell biology and cancer
 
Cancer and genetic influences
Cancer and genetic influences Cancer and genetic influences
Cancer and genetic influences
 
Molecular Genetics of Cancer
Molecular Genetics of CancerMolecular Genetics of Cancer
Molecular Genetics of Cancer
 
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...
 
Oncogenes
Oncogenes Oncogenes
Oncogenes
 
Hereditary Cancer Syndrome
Hereditary Cancer SyndromeHereditary Cancer Syndrome
Hereditary Cancer Syndrome
 
Oncoproteins
OncoproteinsOncoproteins
Oncoproteins
 
Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs
Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs
Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs
 
Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.
 
Cancer genome (2)
Cancer genome (2)Cancer genome (2)
Cancer genome (2)
 
7.Cancer Genetics.Oct.09
7.Cancer Genetics.Oct.097.Cancer Genetics.Oct.09
7.Cancer Genetics.Oct.09
 
Oncogene and tumor suppressor gene
Oncogene and tumor suppressor geneOncogene and tumor suppressor gene
Oncogene and tumor suppressor gene
 
Chapter 2 molecular methods in cancer
Chapter 2 molecular methods in cancerChapter 2 molecular methods in cancer
Chapter 2 molecular methods in cancer
 

Viewers also liked

Molecular Genetics and Cancer Biology
Molecular Genetics and Cancer BiologyMolecular Genetics and Cancer Biology
Molecular Genetics and Cancer BiologyMeshari Alzahrani
 
Molecular Basis of Cancer
 Molecular Basis of Cancer Molecular Basis of Cancer
Molecular Basis of CancerMohsin Shad
 
Introduction cancer genetics and genomics
Introduction cancer genetics and genomicsIntroduction cancer genetics and genomics
Introduction cancer genetics and genomicsNuria Lopez-Bigas
 
Cell cycle and molecular basis of cancer.
Cell cycle and molecular basis of cancer.Cell cycle and molecular basis of cancer.
Cell cycle and molecular basis of cancer.Dr Durga Gahlot
 
4. molecular basis of cancer dr. sinhasan, mdzah
4. molecular basis of cancer  dr. sinhasan, mdzah4. molecular basis of cancer  dr. sinhasan, mdzah
4. molecular basis of cancer dr. sinhasan, mdzahkciapm
 
Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...
Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...
Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...Health Sciences North | Horizon Santé Nord
 
Cancer Biology
Cancer BiologyCancer Biology
Cancer BiologyPhil Mayor
 
The cell cycle and cancer
The cell cycle and cancerThe cell cycle and cancer
The cell cycle and cancerSofia Paz
 
Cell cycle checkpoints, apoptosis and cancer
Cell cycle checkpoints, apoptosis and cancerCell cycle checkpoints, apoptosis and cancer
Cell cycle checkpoints, apoptosis and cancerSurender Rawat
 
Biology And Pathophysiology Of Cancer
Biology And Pathophysiology Of CancerBiology And Pathophysiology Of Cancer
Biology And Pathophysiology Of CancerRHMBONCO
 
Carcinogenesis
CarcinogenesisCarcinogenesis
CarcinogenesisEjaz Waris
 
As Bases genéticas do Câncer
As Bases genéticas do CâncerAs Bases genéticas do Câncer
As Bases genéticas do CâncerAmanda Gerardel
 
Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...
Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...
Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...Fundación Ramón Areces
 
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016Oxford University Press
 

Viewers also liked (20)

Molecular basis of Cancer
Molecular basis of CancerMolecular basis of Cancer
Molecular basis of Cancer
 
Molecular Genetics and Cancer Biology
Molecular Genetics and Cancer BiologyMolecular Genetics and Cancer Biology
Molecular Genetics and Cancer Biology
 
Molecular Basis of Cancer
 Molecular Basis of Cancer Molecular Basis of Cancer
Molecular Basis of Cancer
 
Introduction cancer genetics and genomics
Introduction cancer genetics and genomicsIntroduction cancer genetics and genomics
Introduction cancer genetics and genomics
 
Cancer - Molecular basis
Cancer - Molecular basisCancer - Molecular basis
Cancer - Molecular basis
 
Cell cycle and molecular basis of cancer.
Cell cycle and molecular basis of cancer.Cell cycle and molecular basis of cancer.
Cell cycle and molecular basis of cancer.
 
4. molecular basis of cancer dr. sinhasan, mdzah
4. molecular basis of cancer  dr. sinhasan, mdzah4. molecular basis of cancer  dr. sinhasan, mdzah
4. molecular basis of cancer dr. sinhasan, mdzah
 
Hereditary Cancer Predisposition
Hereditary Cancer PredispositionHereditary Cancer Predisposition
Hereditary Cancer Predisposition
 
Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...
Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...
Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, D...
 
Cancer Biology
Cancer BiologyCancer Biology
Cancer Biology
 
The Cell Cycle and Cancer
The Cell Cycle and CancerThe Cell Cycle and Cancer
The Cell Cycle and Cancer
 
The cell cycle and cancer
The cell cycle and cancerThe cell cycle and cancer
The cell cycle and cancer
 
Cell cycle checkpoints, apoptosis and cancer
Cell cycle checkpoints, apoptosis and cancerCell cycle checkpoints, apoptosis and cancer
Cell cycle checkpoints, apoptosis and cancer
 
Biology And Pathophysiology Of Cancer
Biology And Pathophysiology Of CancerBiology And Pathophysiology Of Cancer
Biology And Pathophysiology Of Cancer
 
Carcinogenesis
CarcinogenesisCarcinogenesis
Carcinogenesis
 
As Bases genéticas do Câncer
As Bases genéticas do CâncerAs Bases genéticas do Câncer
As Bases genéticas do Câncer
 
Cancer Powerpoint
Cancer PowerpointCancer Powerpoint
Cancer Powerpoint
 
Oncology
OncologyOncology
Oncology
 
Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...
Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...
Ana Ramírez de Molina-El impacto de las ciencias ómicas en la medicina, la nu...
 
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016
 

Similar to An Overview of Cancer Genetics

Am 7.15 shulman
Am 7.15 shulmanAm 7.15 shulman
Am 7.15 shulmanplmiami
 
Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...
Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...
Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...European School of Oncology
 
Using biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumorUsing biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumorsummer elmorshidy
 
Prognostic markers on Breast Cancer
Prognostic markers on Breast CancerPrognostic markers on Breast Cancer
Prognostic markers on Breast Cancerabizarl
 
Thyroid tumors varun
Thyroid tumors varunThyroid tumors varun
Thyroid tumors varunVarun Goel
 
Molecular mechanism of neoplasia
Molecular mechanism of neoplasiaMolecular mechanism of neoplasia
Molecular mechanism of neoplasiaUtkarsh Sharma
 
Alain Toledano : Test and genomic profile : what future in breast cancer trea...
Alain Toledano : Test and genomic profile : what future in breast cancer trea...Alain Toledano : Test and genomic profile : what future in breast cancer trea...
Alain Toledano : Test and genomic profile : what future in breast cancer trea...breastcancerupdatecongress
 
Right vs Left Sidedness in Colon Cancer.pptx
Right vs Left Sidedness in Colon Cancer.pptxRight vs Left Sidedness in Colon Cancer.pptx
Right vs Left Sidedness in Colon Cancer.pptxDrMalcolmBrigden1
 
triple negative breast cancer
triple negative breast cancertriple negative breast cancer
triple negative breast cancerLuis Toache
 
Molecular testing and ihc surrogates for breast carcinoma
Molecular testing and ihc surrogates for breast carcinomaMolecular testing and ihc surrogates for breast carcinoma
Molecular testing and ihc surrogates for breast carcinomaKasturba Medical College
 

Similar to An Overview of Cancer Genetics (20)

Am 7.15 shulman
Am 7.15 shulmanAm 7.15 shulman
Am 7.15 shulman
 
Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...
Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...
Rare Solid Cancers: An Introduction - Slide 9 - G. Rosti - Rare male genital ...
 
Using biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumorUsing biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumor
 
Prognostic markers on Breast Cancer
Prognostic markers on Breast CancerPrognostic markers on Breast Cancer
Prognostic markers on Breast Cancer
 
Prostate updates
Prostate updatesProstate updates
Prostate updates
 
Prostate cancer
Prostate cancerProstate cancer
Prostate cancer
 
Fibromatosis
FibromatosisFibromatosis
Fibromatosis
 
Carcinoma Anaplasico de tiroides
Carcinoma Anaplasico de tiroidesCarcinoma Anaplasico de tiroides
Carcinoma Anaplasico de tiroides
 
Thyroid tumors varun
Thyroid tumors varunThyroid tumors varun
Thyroid tumors varun
 
Molecular mechanism of neoplasia
Molecular mechanism of neoplasiaMolecular mechanism of neoplasia
Molecular mechanism of neoplasia
 
Lehrach
LehrachLehrach
Lehrach
 
Prostate cancer
Prostate cancer Prostate cancer
Prostate cancer
 
20160218 hisham toma services
20160218 hisham toma services20160218 hisham toma services
20160218 hisham toma services
 
Alain Toledano : Test and genomic profile : what future in breast cancer trea...
Alain Toledano : Test and genomic profile : what future in breast cancer trea...Alain Toledano : Test and genomic profile : what future in breast cancer trea...
Alain Toledano : Test and genomic profile : what future in breast cancer trea...
 
C&C.pptx
C&C.pptxC&C.pptx
C&C.pptx
 
2015 fellows lecture version d
2015 fellows lecture version d2015 fellows lecture version d
2015 fellows lecture version d
 
Right vs Left Sidedness in Colon Cancer.pptx
Right vs Left Sidedness in Colon Cancer.pptxRight vs Left Sidedness in Colon Cancer.pptx
Right vs Left Sidedness in Colon Cancer.pptx
 
triple negative breast cancer
triple negative breast cancertriple negative breast cancer
triple negative breast cancer
 
PIIS0016508514604509
PIIS0016508514604509PIIS0016508514604509
PIIS0016508514604509
 
Molecular testing and ihc surrogates for breast carcinoma
Molecular testing and ihc surrogates for breast carcinomaMolecular testing and ihc surrogates for breast carcinoma
Molecular testing and ihc surrogates for breast carcinoma
 

More from Dana-Farber Cancer Institute

Personal Finance Tips for Young Adults with Cancer
Personal Finance Tips for Young Adults with Cancer Personal Finance Tips for Young Adults with Cancer
Personal Finance Tips for Young Adults with Cancer Dana-Farber Cancer Institute
 
How are Adult and Childhood Leukemia Alike and Different?
How are Adult and Childhood Leukemia Alike and Different?How are Adult and Childhood Leukemia Alike and Different?
How are Adult and Childhood Leukemia Alike and Different?Dana-Farber Cancer Institute
 
Research in the Program for Young Women with Breast Cancer: Past, Present and...
Research in the Program for Young Women with Breast Cancer: Past, Present and...Research in the Program for Young Women with Breast Cancer: Past, Present and...
Research in the Program for Young Women with Breast Cancer: Past, Present and...Dana-Farber Cancer Institute
 
Clinical Trials for Metastatic HER2-positive Breast Cancer
Clinical Trials for Metastatic HER2-positive Breast CancerClinical Trials for Metastatic HER2-positive Breast Cancer
Clinical Trials for Metastatic HER2-positive Breast CancerDana-Farber Cancer Institute
 
Clinical Trials for Metastatic Triple-Negative Breast Cancer
Clinical Trials for Metastatic Triple-Negative Breast CancerClinical Trials for Metastatic Triple-Negative Breast Cancer
Clinical Trials for Metastatic Triple-Negative Breast CancerDana-Farber Cancer Institute
 
Surgery for Inflammatory Breast Cancer: How and Why
Surgery for Inflammatory Breast Cancer: How and WhySurgery for Inflammatory Breast Cancer: How and Why
Surgery for Inflammatory Breast Cancer: How and WhyDana-Farber Cancer Institute
 
Primary Systemic Therapy for Inflammatory Breast Cancer
Primary Systemic Therapy for Inflammatory Breast CancerPrimary Systemic Therapy for Inflammatory Breast Cancer
Primary Systemic Therapy for Inflammatory Breast CancerDana-Farber Cancer Institute
 
7 Ways Integrative Therapies Can Help Cancer Patients
7 Ways Integrative Therapies Can Help Cancer Patients7 Ways Integrative Therapies Can Help Cancer Patients
7 Ways Integrative Therapies Can Help Cancer PatientsDana-Farber Cancer Institute
 

More from Dana-Farber Cancer Institute (20)

Exercise Tips for Cancer Patients
Exercise Tips for Cancer Patients Exercise Tips for Cancer Patients
Exercise Tips for Cancer Patients
 
Personal Finance Tips for Young Adults with Cancer
Personal Finance Tips for Young Adults with Cancer Personal Finance Tips for Young Adults with Cancer
Personal Finance Tips for Young Adults with Cancer
 
5 Things to Know About Glioblastomas
5 Things to Know About Glioblastomas5 Things to Know About Glioblastomas
5 Things to Know About Glioblastomas
 
How are Adult and Childhood Leukemia Alike and Different?
How are Adult and Childhood Leukemia Alike and Different?How are Adult and Childhood Leukemia Alike and Different?
How are Adult and Childhood Leukemia Alike and Different?
 
Research in the Program for Young Women with Breast Cancer: Past, Present and...
Research in the Program for Young Women with Breast Cancer: Past, Present and...Research in the Program for Young Women with Breast Cancer: Past, Present and...
Research in the Program for Young Women with Breast Cancer: Past, Present and...
 
Clinical Trials for Metastatic HER2-positive Breast Cancer
Clinical Trials for Metastatic HER2-positive Breast CancerClinical Trials for Metastatic HER2-positive Breast Cancer
Clinical Trials for Metastatic HER2-positive Breast Cancer
 
Clinical Trials for Metastatic Triple-Negative Breast Cancer
Clinical Trials for Metastatic Triple-Negative Breast CancerClinical Trials for Metastatic Triple-Negative Breast Cancer
Clinical Trials for Metastatic Triple-Negative Breast Cancer
 
Healthy Living After A Breast Cancer Diagnosis
Healthy Living After A Breast Cancer DiagnosisHealthy Living After A Breast Cancer Diagnosis
Healthy Living After A Breast Cancer Diagnosis
 
Signs and Symptoms of Prostate Cancer
Signs and Symptoms of Prostate CancerSigns and Symptoms of Prostate Cancer
Signs and Symptoms of Prostate Cancer
 
6 Common Types of Pediatric Brain Tumors
6 Common Types of Pediatric Brain Tumors6 Common Types of Pediatric Brain Tumors
6 Common Types of Pediatric Brain Tumors
 
Soft Tissue Sarcomas: Symptoms and Risk Factors
Soft Tissue Sarcomas: Symptoms and Risk FactorsSoft Tissue Sarcomas: Symptoms and Risk Factors
Soft Tissue Sarcomas: Symptoms and Risk Factors
 
10 Tips for Easing Chemo-Related Fatigue
10 Tips for Easing Chemo-Related Fatigue10 Tips for Easing Chemo-Related Fatigue
10 Tips for Easing Chemo-Related Fatigue
 
Surgery for Inflammatory Breast Cancer: How and Why
Surgery for Inflammatory Breast Cancer: How and WhySurgery for Inflammatory Breast Cancer: How and Why
Surgery for Inflammatory Breast Cancer: How and Why
 
Radiation Therapy for Inflammatory Breast Cancer
Radiation Therapy for Inflammatory Breast CancerRadiation Therapy for Inflammatory Breast Cancer
Radiation Therapy for Inflammatory Breast Cancer
 
Primary Systemic Therapy for Inflammatory Breast Cancer
Primary Systemic Therapy for Inflammatory Breast CancerPrimary Systemic Therapy for Inflammatory Breast Cancer
Primary Systemic Therapy for Inflammatory Breast Cancer
 
What Cancers Should Men Be Screened For?
What Cancers Should Men Be Screened For?What Cancers Should Men Be Screened For?
What Cancers Should Men Be Screened For?
 
Five Common Types of Brain Tumors
Five Common Types of Brain TumorsFive Common Types of Brain Tumors
Five Common Types of Brain Tumors
 
Signs and Symptoms of Multiple Myeloma
Signs and Symptoms of Multiple MyelomaSigns and Symptoms of Multiple Myeloma
Signs and Symptoms of Multiple Myeloma
 
7 Ways Integrative Therapies Can Help Cancer Patients
7 Ways Integrative Therapies Can Help Cancer Patients7 Ways Integrative Therapies Can Help Cancer Patients
7 Ways Integrative Therapies Can Help Cancer Patients
 
Five Things You Need to Know About Colon Cancer
Five Things You Need to Know About Colon CancerFive Things You Need to Know About Colon Cancer
Five Things You Need to Know About Colon Cancer
 

Recently uploaded

Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyZurück zum Ursprung
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptPradnya Wadekar
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptxORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptxNIKITA BHUTE
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfHongBiThi1
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communicationskatiequigley33
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionkrishnareddy157915
 

Recently uploaded (20)

Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturally
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologyppt
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptxORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptx
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communications
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung function
 

An Overview of Cancer Genetics

  • 1. Cancer Genetics Judy E. Garber, MD MPH Director, Cancer Genetics and Prevention Dana-Farber Cancer Institute
  • 3. Cancer is a Genetic Disease Normal cells and Cancer cells contain the same 30,000 genes what distinguishes them is which of the genes are turned on and off Normal Cancer Which genes are activated in cancer?
  • 4. Chromosomes, DNA, and Genes Gene Nucleus Cell Chromosomes Protein Adapted from Understanding Gene Testing, NIH, 1995
  • 5. The DNA Double Helix Sugar phosphate Base pair backbone Bases Adenine (A) Cytosine (C) Thymine (T) Guanine (G)
  • 6. Normal Male Karyotype p Centromere q Chromosome 5
  • 7. Genetic Code A codon is made of 3 base pairs 64 codons total 1 codon (AUG) encodes 61 codons encode 3 codons stop methionine and starts 20 amino acids protein translation of all proteins (redundant code) translation A U G G C A U A A Met Ala
  • 8. Disease-Associated Mutations Alter Protein Function Functional protein Nonfunctional or missing protein
  • 9. Autosomal Dominant Inheritance  Each child has 50% chance of inheriting the mutation  No “skipped generations”  Equally transmitted by men and women Unaffected Affected
  • 10. The Two-Hit Hypothesis First hit First hit in Second hit germline (tumor)
  • 11. Tumor Suppressor Genes Normal genes (prevent cancer) 1st mutation (susceptible carrier) 2nd mutation or loss (leads to cancer)
  • 12. Oncogenes Normal genes (regulate cell growth) 1st mutation (leads to accelerated cell division) 1 mutation sufficient for role in cancer development
  • 13. Normal (male) chromosomes and BRCA1-deficient cancer cells with gross chromosomal abnormalities
  • 15. More Subtle Pedigrees PR 60 CO 61? 55* OV 59 BR 32 BR 34 *TAH/BSO at 40
  • 16. Genetic Testing 2012 • Genetic testing requires a DNA sample from blood, saliva or other tissue • Testing costs are usually covered by health insurance, at least partially • Laws to prevent discrimination in health insurance exist (GINA) • Testing is often offered at the time of cancer diagnosis, because the information can affect management decisions • Autonomy and Access are still important
  • 17. +
  • 18. Once the mutation is found in one person in the family after full price testing, the rest of the family can be tested to see whether they do or do NOT share the mutation. The “single site” testing is usually about $500.
  • 19. BR/OV Cancer Risk Management Options for BRCA Mutation Carriers Surveillance (does not  risk) • Mammogram, MRI, Exam, +/- US • (TransVaginal Ultrasound, CA125) Chemoprevention • Tamoxifen/ Raloxifene? Exemestane? Other? • Birth Control Pills  Ov ca risk Prophylactic Surgery • 90% Bilateral mastectomy • Removal ovaries & fallopian tubes: 90% Ov ca risk; if done premenopausal, ~50%  BrCa risk
  • 20. I’M OUT OF ESTROGEN AND I AM NOT HAPPY ABOUT IT
  • 21. Risk of Colorectal Cancer (CRC) General population 5% Personal history of colorectal neoplasia 15%–20% Inflammatory 15%–40% bowel disease HNPCC mutation 70%–80% FAP >95% 0 20 40 60 80 100 Lifetime risk (%)
  • 22. Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch Syndrome) • Colon, Uterine and other cancers • In HNPCC, the tumor CO 45 UT 38 tissue stored in a CO 40 pathology department _ + can be studied for evidence that the CO 28 Cecum 35 syndrome is present, so ST 32 even a deceased relative can be informative 4
  • 23. A Li - F raum eni S yndrom e K indred C R C , 72 Lung, 48 80 O S , 14 Laryn x, 56 B reast, 26 B reast, 22, 27 S T S , 33* S tom ach, 32 B reast, 32 ACC, 5 O S , 14 S T S , 26* * tum or in R T field of prior m alig na ncy
  • 25. FDG-PET/CT Screening in LFS Results Fused PET/CT CT
  • 26. Survival of TP53 Mutation Carriers in Surveillance and Non-Surveillance Groups Villani A et al. Lancet Oncol 2011;12:559-567
  • 27. Decisions Potentially Influenced by BRCA1/2 Status in Breast Cancer Patients • Management of newly diagnosed patients – Primary Therapy: Surgical Options – Chemotherapy – Hormonal therapy • Management of breast cancer survivors – Additional primary breast cancer risk – Ovarian cancer risk – Treatment of metastatic disease • Implications for Relatives
  • 28. Breast Cancer Subtypes are Associated with Different Germline Mutations ER+ PR+/HER2- BRCA2, TP53 ER+ or ER-/HER2+ TP53 ER-, PR-, HER2- BRCA1
  • 29. Kaplan-Meier estimates of recurrence-free survival and overall survival after neoadjuvant T-FAC by : BRCA status Path CR TNBC Arun B et al. J Clin Oncol 2011;29:3739-3746
  • 30. -
  • 31. Expanded Commercial Cancer Genetic Testing is Here
  • 32. TP53 Germline Deletion in Patient With t-AML BR 37 + OV 39 R-OV 42 AML 42 3 Link DC et al. JAMA 2011;305:1568-1576
  • 35. A Paradigm Shift – The Genomic View of Cancer From Anatomy… From KIT Germline (Imatinib) • Lung Tumor Blood Genomic Genomic • Breast Profiling EGFR Profiling (Erlotinib) •Prostate HER2 (Trastuzumab) • Colon BRAF (PLX4032) • Brain PIK3CA (BEZ235)
  • 36. Potential Findings from Sequencing DNA from Tumor & Blood of DFCI Cancer Patients in PCMP • Tumor genome: treatment targets, predictors of response • Personal genome: • Variation in drug metabolizing genes that affect dose or choice of agent • Mutations in genes that confer  risk of the patient’s cancer and related cancers (e.g, BRCA, HNPCC), important to patient and family • Mutations in genes associated with Non-Cancer conditions that could be more important to relatives (e.g., long QT; Fragile X)
  • 39. Learn more about the DFCI Gene Display. Gene Display in the Yawkey Center for Cancer Care
  • 40. Audience Q&A What about people who are adopted and don’t know anything about their family history?
  • 41. Audience Q&A What is does the insurance industry think about preventative surgeries?
  • 42. Audience Q&A For insurance purposes, do you have to build a case to justify preventative surgery based on genetic testing?
  • 43. Resources and Additional Information • Check out the Cancer Genetics and Prevention Program at Dana-Farber. • Watch Dr. Judy Garber discuss her work as the director of Cancer Genetics and Prevention Program. • View more resources available through DFCI for patients and families dealing with cancer. To schedule an appointment at DFCI, click here.