Advances in Population Genetics and Hereditary Prediction Models for Pancreatic Cancer
|
|
- Chrystal Harper
- 5 years ago
- Views:
Transcription
1 Advances in Population Genetics and Hereditary Prediction Models for Pancreatic Cancer Gloria M. Petersen, Ph.D. Department of Health Sciences Research Mayo Clinic Rochester, Minnesota Pancreasfest
2 Take Home Messages 1. Pancreatic cancer susceptibility gene discovery has uncovered new insights and has matured to translation. 2. Patients with and without positive family history can carry germline mutations in an array of genes. 3. Risk modeling for pancreatic cancer using genomic data remains a work in progress.
3 Complex Diseases: Genetic Variants of Different Effect Manolio, T et al. Finding the missing heritability of complex diseases. Nature 2009 October 8; 461(7265): McCarthy MI, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nature Rev. Genet. 2008;9:
4 Gene discovery in pancreatic cancer Subjects Design Genetic analysis technology Discovery goal Familial Cases Probands and/or family members Whole genome/exome sequencing Linkage marker genotyping Rare susceptibility genes with high effect (penetrance) Sporadic Cases Cases only Whole genome/exome sequencing Susceptibility genes, rare or moderate frequency with high effect Sporadic Cases & Healthy Controls Case-control association study (GWAS) Genome wide SNP panels Common variants with low effect
5 Genetics of Pancreatic Cancer: Families 10% of pancreatic cancer patients have a first degree relative with pancreatic cancer Positive Family History
6 Factors Influencing Pancreatic Cancer Risk Age older age Smoking Family History Race - Black High BMI, Obesity Hx Diabetes Hx Chronic Pancreatitis Heavy alcohol use Short telomeres Risk X X X X X X X X X Protective
7 Factors Influencing Pancreatic Cancer Risk Allergies Aspirin Use Diet Well-done, BBQ meat Fruits, vegetables, fiber Pesticides, benzene, asbestos, chlorinated hydrocarbons Risk X X Protective X X X
8 Pancreatic cancer risk in first degree relatives Case-Control studies Authors Cases Controls OR (95% C.I.) Falk et al. (1988) 362 1, ( ) Fernandez et al. (1994) 363 1, ( ) Silverman et al. (1999) 484 2, ( ) Schenk et al. (2001) ( ) Prospective Number of Affected First Degree Relatives SIR (95% CI) ( ) ( ) ( ) Klein AP, Brune KA, Petersen GM, et al.. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004; 64: Axilbund,J, Wiley E. Genetic Testing by Cancer Site: Pancreas. Cancer Journal. 18(4): , 2012.
9 Inherited Susceptility to Pancreatic Cancer: Updated HBOC Peutz Jeghers Syndrome Hereditary pancreatitis Familial atypical mole and melanoma Hereditary nonpolyposis colorectal cancer (Lynch syndrome) HBOC Klein AP. Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer Jan;13(1):66-74.
10 Zhen DB et al. Prevalence of BRCA1, BRCA2, PALB2, and CDKN2A Mutations in Familial Pancreatic Cancer (FPC): A PACGENE Study. Genetics in Medicine, 2015 Jul;17: Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium sites assembled 2,853 unrelated kindreds containing at least two family members affected with pancreatic cancer. 727 unrelated kindreds that contained at least two biologically related family members affected with pancreatic cancer and for which a proband DNA sample was available.
11 Table 3. Germline mutation prevalences stratified by deleterious/suspected deleterious and variants of uncertain significance among probands from Familial Pancreatic Cancer (FPC) kindreds, and probands from kindreds not meeting FPC definition. Results shown for probands who were tested for all four genes (total n=716). Gene Deleterious/Suspected Deleterious Mutations n (%) FPC (n=515) Non-FPC (n=201) Total (n=716) Variants of Uncertain Significance n (%) FPC (n=515) Non-FPC (n=201) Total (n=716) BRCA1 6 (1.2) 0 (0.0) 6 (0.8) 3 (0.6) 0 (0.0) 3 (0.4) BRCA2 19 (3.7) 6 (3.0) 25 (3.5) 2 (0.4) 1 (0.5) 3 (0.4) PALB2 3 (0.6) 1 (0.5) 4 (0.6) 11 (2.1) 5 (2.5) 16 (2.2) CDKN2A 13 (2.5) 0 (0.0) 13 (1.8) 10 (1.9) 3 (1.5) 13 (1.8) Total 41 (8.0) 7 (3.5) 48 (6.7) 26 (5.0) 9 (4.5) 35 (4.9) Zhen DB et al. Genetics in Medicine, 2015 Jul;17:569-77
12 Figure 1. Probability (%) that probands affected with pancreatic cancer (PC) will test positive for a deleterious or suspected deleterious mutation in BRCA1, BRCA2, PALB2, or CDKN2A, if from kindreds with various cancer family histories. Number of PC includes proband. Size of sample subsets from which probabilities were estimated are shown in parentheses. (727 probands tested) Zhen DB et al. Genetics in Medicine, 2015 Jul;17:569-77
13 Mayo Clinic study of mutations in 25 genes (ASCO 2016) Germline pathogenic variant prevalence by type of familial proband (FPC vs familial Non-FPC), categorized by genes associated and not associated with PDAC. Genes with no pathogenic variants included APC, BMPR1A, BRIP1, CDH1, CDK4, EPCAM/TACSTD1, MLH1, MSH2, MSH6, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53. FPC (n=186) Non-FPC (n=117) Total (n=303) N % N % N % All Genes Genes Associated with PDAC ATM BRCA BRCA CDKN2A (p16) PALB PMS Sub-Total* Genes Not Associated with PDAC BARD CHEK MUTYH/MYH NBN Sub-Total * One FPC case carried two pathogenic variants: one in BRCA1 and one in BRCA2.
14 Smith AL Gallinger S, Zogopoulos G. Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer. Cancer Lett Jan 28;370(2): Search for novel DNA repair susceptibility genes for pancreatic cancer using whole exome sequencing 109 high-risk PC cases from Ontario or Quebec PC research registries Young - dx d <50 years (N=8) Familial PC (N=101 in 85 kindreds) Known mutation carriers excluded 513 genes: putative DNA repair genes plus CDKN2A, SPINK1 and PRSS1 Private truncating variants (PTVs) in 41 novel genes among 36 kindreds.
15 Top Candidate Novel Susceptibility Genes AATF BLM CEP164 CHD1L FAN1 FANCG FANCL MCIR MGMT NEIL1 NEK1 NEK11 RHNO1 SPP1 TONSL WDR48 WRN Smith AL, et al. Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer. Cancer Lett Nov 3.
16 A PACGENE study Sequenced whole genomes of 638 familial pancreatic cancer patients from 593 kindreds Sequenced exomes of pancreatic adenocarcinomas from 39 of these same patients. Strongly support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, p16/cdkn2a and ATM, and identify candidate genes harboring rare, deleterious germline variants for further characterization. Roberts NJ et al. Cancer Discovery 6:166-75, 2015
17 Genetics of Pancreatic Cancer: Sporadic Positive Family History
18 PanScan GWAS (Wave 1) Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nature Genetics 41:986-90, pairs Petersen GM, Amundadottir A, Fuchs CS, et al. A genomewide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p Nature Genetics, 42:224-8, pairs
19 GWAS Wave 2: Wolpin B et al. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nature Genetics 46 (9): , PanScan3 7,683 pancreatic cancer 14,397 publicly available data on controls GWAS Wave 3. Childs EJ et al. (PANC4 study). Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nature Genetics, 47:911-6, cases and 11,569 controls including 4,164 newly genotyped cases and 3,792 controls controls in 9 study populations from N. America, Central Europe and Australia. GWAS Wave 4. Childs EJ et al. Association of common susceptibility variants of pancreatic cancer in higher risk patients: A PACGENE Study. Cancer Epidemiol Biomarkers Prev Jul;25(7): cases (906 FPC; 79 early onset; 877 family controls) icogs array plus custom SNPs
20 Manhattan plot of Combined Stage 1 Association analysis. Novel loci associated with pancreatic cancer in Caucasians shown in red. (ABO) (Nongenic) (NR5A2) (CLPTM1L-TERT) (LINC00673) Childs EJ et al. (PANC4 study). Nature Genetics 47:911-6, 2015.
21 Pancreatic Cancer and CDKN2A Methods: 1,537 pancreatic adenocarcinoma patients Consecutive, unselected white non-hispanic patients Lymphocyte DNA; exons and splice sites sequenced for CDKN2A Results: 9 (0.6%) carried germline mutations in CDKN2A 3 mutations previously unreported: missense mutation in p14 (A120P) and two frameshift mutations that affect both p16 and p14arf (R80fs/ P135fs and V95fs/ G150fs) CDKN2A mutation carriers were more likely to have: family hx pancreatic cancer (p= 0.003); carrier rate 3.3% family hx melanoma (p= 0.03); carrier rate 5.3% personal hx melanoma (p= 0.01) McWilliams RR et al. Eur J Hum Genetics, 2011 Apr;19(4):472-8.
22 Germline Mutations in CDKN2A Among 1,537 Unselected Unrelated Pancreatic Cancer Patients Pt Sex/ Age* Family history of pancreatic cancer Family history of melanoma Personal history of melanoma Exon Protein Genetic change Protein change Function 1 F 61 Yes No No 1A p16-34g>t N/A Initiation codon 2 M 74 No Yes Yes 1A p16 47T>G L16>R AAC p16 3 F 65 No No No 1A p16 71G>C R24>P AAC p16 4 F 58 No No No 2 p16 p14 5 M 66 No No No 2 p16 p14 192G>C 358G>C del del L64>L A120>P R80fs P135fs AAC p14arf makes a hybrid p16/p14 protein after frameshift 6 M 65 Yes No No 2 p16 p del 449 del V95fs G150fs frameshift 7 M 45 No No No 2 p16 p14 318G>A 484G>A V106>V A162>T AAC p14arf 8 M 67 No Yes Yes 2 p16 457G>T D153spl Affects splicing in p16/p14arf 9 M 57 Yes No No 2 p16 457G>T D153spl Affects splicing in p16/p14arf * M= male, F=female, age (years) at diagnosis of pancreatic cancer, AAC = amino acid change McWilliams RR et al. Eur J Hum Genetics, 2011 Apr;19(4):472-8.
23 Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients With Pancreatic Cancer Grant R et al. Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients With Pancreatic Cancer. Gastroenterology 2015;148:
24 Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients. Hu C, Hart SN, Bamlet WR, Moore RM, Nandakumar K, Eckloff BW, Lee YK, Petersen GM, McWilliams RR, Couch FJ. Cancer Epi Biomarkers and Prevention, 2016 Jan;25(1): patients unselected for a family history of cancer who were recruited to the Mayo Clinic Pancreatic Cancer patient registry over a 12 month period Panel of 21 cancer predisposition genes Next-generation sequencing
25 Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients. Hu C, Hart SN, Bamlet WR, Moore RM, Nandakumar K, Eckloff BW, Lee YK, Petersen GM, McWilliams RR, Couch FJ.Cancer Epi Biomarkers and Prevention, 2016 Jan;25(1): Fourteen pathogenic mutations in eight genes were identified in 13 patients (13.5%). One patient carried mutations in both NBN and CHEK2. Gene Nucleotide Age# Personal history of other cancer (age at diagnosis) Cancer in 1 st and 2 nd degree relatives b ATM c.2880delc 64 None 3 colorectal Meets NCCN Criteria for Cancer Syndrome? ATM c.5932g>t 83 Breast (67) 1 breast ATM c.6012_6013insa 66 Liver (66) None ATM c.7327c>t 67 Unknown (67) 1 pancreatic BARD1 c.1921c>t 71 None 1 pancreatic BRCA1 c.212+1g>a 59 None 2 breast, 1 pancreatic Yes (HBOC) BRCA2 c.5864c>a 69 None 1 breast Yes (HBOC) BRCA2 c.6373dupa 51 None 2 pancreatic, 2 breast, 1 endometrial Yes (HBOC) CHEK2 c.1100delc 79 None None FANCM c.2586_2589delaaaa 76 Melanoma 2 breast, 1 pancreatic MSH6 c.3804dupa 63 Endometrial (43) 2 breast, 2 colorectal Yes (Lynch) MSH6 c _ del25 75 None 1 breast No (Lynch) NBN/CHEK2 c.657_661del5/1100delc 80 None None
26 Assessment of germline cancer predisposition genes in 392 unselected pancreatic cancer patients. McKay S, Humphris J, Johns A, Pinese M, Patch A, Nones K, APGI, Grimmond S, Biankin A. Abstract A02, AACR Conference on Pancreatic Cancer: Advances in Science and Clinical Care, May 12-15, Patients 13 genes analyzed among data from WES (n=208)and WGS (n=184) 23 (5.9%) patients classified as pathogenic or likely pathogenic carriers 3/23 were familial cases No mutations found in: APC, MLH1, MSH2, MSH6, PRSS1, or TP53
27 RISK MODELING THAT INCORPORATES GENETIC INFORMATION Klein AP et al. An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PLoS One Sep 13;8(9):e Data on 3,349 cases and 3,654 controls from the PanScan Consortium Non-genetic and genetic risk factors for pancreatic cancer Absolute risks estimated based on relative risks and population incidence rates: Variable Multivariable OR [95% CI] Current smoking 2.20 [ ] Family history of pancreatic cancer 1.60 [ ] Obesity (body mass index >30 kg/m 2 ) 1.26 [ ] Non-O ABO genotype AO vs. OO genotype BB vs. OO genotype ABO genetic SNPs rs (chr1q32.1) rs401681(5p15.33) rs (13q22.1) ( Diabetes >3 years Nested case-control Case-control 1.23 [ ] 1.58 [ ] 1.29 [ [ ] 1.27 [ ] 1.57 [ ] 1.80 [ ] Heavy alcohol use (>3 drinks/day) 1.45 [ ]
28 Klein AP et al. An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PLoS One Sep 13;8(9):e AUC for risk models: Only non-genetic factors: 58% Only genetic factors: 57% Both non-genetic and genetic factors: 61% Fewer than 3/1,000 U.S. non- Hispanic whites have more than a 5% predicted lifetime absolute risk. immediate clinical utility of model is limited. The genetic factors did not add substantively to a risk model based on life-style factors only, as most individuals remained in the same risk strata.
29 Klein AP et al. An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PLoS One Sep 13;8(9):e72311.
30
31 Take Home Messages 1. Pancreatic cancer susceptibility gene discovery has uncovered new insights and has matured to translation. 2. Patients with and without positive family history can carry germline mutations in an array of genes. 3. Risk modeling for pancreatic cancer using genomic data remains a work in progress.
32 Collaborators & Acknowledgments Mayo Clinic Rob McWilliams, MD Kari Chaffee, M.S. Suresh Chari, M.D. Hugues Sicotte, Ph.D. Fergus Couch, Ph.D. Julie Cunningham, Ph.D. Thomas Smyrk, M.D. Bill Bamlet, M.S. Lizhi Zhang, M.D. Martin Fernandez-Zapico, MD PanC4 GWAS Leadership Team: Harvey Risch, Ph.D., Yale Sara Olson, Ph.D., MSKCC Donghui Li, Ph.D., MDACC Steve Gallinger, MD, OICR Federico Canzian, PhD, DKFZ Paige Bracci, UCSF Rachel Neale, Queensland RO1 CA97075 (to GMP) R01 CA (to APK) SPORE (P50 CA ) R01 CA (to GMP, BK, SW) PanCAN CIDR PanScan Project Leadership Team: Patricia Hartge, Sc.D, NCI/DCEG Robert Hoover, M.D., Sc.D, NCI/DCEG Stephen Chanock, M.D., NCI/DCEG/CGF Laufey Amundadottir, Ph.D., NCI/CGF/DCEG Brian Wolpin, M.D., Harvard University Charles Fuchs, M.D., M.P.H, Harvard University Charles Kooperberg, Fred Hutchinson CR Peter Kraft, Ph.D., Harvard University Rachael Stolzenberg-Solomon, M.P.H., Ph.D., NCI Kai Yu, Ph.D., NCI Johns Hopkins University Ralph Hruban, M.D. Alison Klein, Ph.D. Mike Goggins, M.D. Mimi Canto, MD Nick Roberts, DVM, PhD PACGENE collaborators Melissa Bondy, Ph.D. MD Anderson/Baylor Steve Gallinger, M.D. Univ Toronto Ann Schwartz, Ph.D. - Wayne State Univ Sapna Syngal, M.D. Dana Farber Cancer Inst Daniela Seminara, Ph.D. NCI
Genetic testing and pancreatic disease
Genetic testing and pancreatic disease February 2 d, 2018 Yale Pancreas Symposium 2018: Multidisciplinary Management of Pancreatic Cancer Xavier Llor, M.D., PhD. Associate Professor of Medicine Co-Director,
More informationGermline Testing for Hereditary Cancer with Multigene Panel
Germline Testing for Hereditary Cancer with Multigene Panel Po-Han Lin, MD Department of Medical Genetics National Taiwan University Hospital 2017-04-20 Disclosure No relevant financial relationships with
More informationWHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins.
WHAT IS A GENE? CHROMOSOME E GEN DNA A gene is made up of DNA. It carries instructions to make proteins. The proteins have specific jobs that help your body work normally. PROTEIN 1 WHAT HAPPENS WHEN THERE
More informationWHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins.
WHAT IS A GENE? CHROMOSOME GENE DNA A gene is made up of DNA. It carries instructions to make proteins. The proteins have specific jobs that help your body work normally. PROTEIN 1 WHAT HAPPENS WHEN THERE
More informationHereditary Aspects of Pancreatic Cancer
Pancreatic Cancer Seminar San Francisco, CA Hereditary Aspects of Pancreatic Cancer Genetic Risk Assessment and Counseling for Familial Pancreatic Cancer February 3, 2016 Amie Blanco, MS, CGC Gordon and
More informationGYNplus: A Genetic Test for Hereditary Ovarian and/or Uterine Cancer
GYNplus: A Genetic Test for Hereditary Ovarian and/or Uterine Cancer Causes of Hereditary Ovarian and Uterine Cancer uterine cancer ovarian cancer Sporadic 75-90% Sporadic 70-80% Hereditary, 5% Lynch syndrome
More informationGYNplus. genetic testing for hereditary ovarian and/or uterine cancer
GYNplus genetic testing for hereditary ovarian and/or uterine cancer What Are the Causes of Hereditary Ovarian and Uterine Cancer? uterine cancer ovarian cancer sporadic 70-80% hereditary 5% Lynch syndrome
More informationWhy Test for Hereditary Cancer in Preventive Care?
Why Test for Hereditary Cancer in Preventive Care? Millions of people are sidelined by cancer. Wouldn't it be worth it for your patients to know their risk? background HEREDITARY (5-10%) More than 1 in
More informationUse of panel tests in place of single gene tests in the cancer genetics clinic
Clin Genet 2015: 88: 278 282 Printed in Singapore. All rights reserved CLINICAL GENETICS doi: 10.1111/cge.12488 Short Report se of panel tests in place of single gene tests in the cancer genetics clinic
More informationA Patient s Guide to Hereditary Cancer. Is Hereditary Cancer Testing Right for You?
A Patient s Guide to Hereditary Cancer Is Hereditary Cancer Testing Right for You? What is Hereditary Cancer? Most cancers occur in people who do not have a strong family history of that cancer. This is
More informationLearn your genetic risk for the most common hereditary cancers.
Learn your genetic risk for the most common hereditary cancers. color.com Color analyzes 30 genes including BRCA1 and BRCA2 to help women and men understand their risk for the most common hereditary cancers,
More informationManaging Moderate Penetrance
Managing Moderate Penetrance Thomas Slavin, MD, FACMG Assistant Clinical Professor, Department of Medical Oncology, Division of Clinical Cancer Genetics Program Member, Cancer Control and Population Sciences
More informationPancreas Cancer Genomics
Pancreas Cancer Genomics Steven Gallinger MD, MSc, FRCS HPB Surgical Oncology Program University Health Network Samuel Lunenfeld Research Institute Mount Sinai Hospital University of Toronto Fate of the
More informationThe Next Generation of Hereditary Cancer Testing
The Next Generation of Hereditary Cancer Testing Why Genetic Testing? Cancers can appear to run in families. Often this is due to shared environmental or lifestyle patterns, such as tobacco use. However,
More informationMultigene Panel Testing for Hereditary Cancer Risk
Multigene Panel Testing for Hereditary Cancer Risk Dana Zakalik, M.D. Director, Nancy and James Grosfeld Cancer Genetics Center Professor, OUWB Medical School MCC Annual Meeting November 4, 2015 Outline
More informationAssessment and Management of Genetic Predisposition to Breast Cancer. Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18
Assessment and Management of Genetic Predisposition to Breast Cancer Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18 Overview The role of the Cancer Genetics team NICE guidelines for Familial Breast
More informationA guide to genetic testing for hereditary cancers
Cancer Testing Solutions A guide to genetic testing for hereditary cancers The benefit of knowing TM Hereditary cancer genetic testing can play a critical role in managing health Cancer touches millions
More informationBRCAplus. genetic testing for hereditary breast cancer
BRCAplus genetic testing for hereditary breast cancer Developed in collaboration with Fox Chase Cancer Center and the Arcadia University Genetic Counseling Program. Causes of Hereditary Breast Cancer familial
More informationCentoCancer STRIVE FOR THE MOST COMPLETE INFORMATION
CentoCancer STRIVE FOR THE MOST COMPLETE INFORMATION CentoCancer our most comprehensive oncogenetics panel for hereditary mutations Hereditary pathogenic variants confer an increased risk of developing
More informationThe benefit of. knowing. Genetic testing for hereditary cancer. A patient support guide
The benefit of knowing Genetic testing for hereditary cancer A patient support guide Does cancer run in your family? Cancer is more common in some families. Sometimes cancer is caused by a change in a
More informationGenetics & Precision Medicine Cancer Care
Genetics & Precision Medicine Cancer Care Johnathan M. Lancaster, MD PhD Chief Medical Officer Myriad Genetics Copyright 2015 Myriad Genetics, Inc., all rights reserved. www.myriad.com. Precision Medicine
More informationThe Role of genetic Testing for Inherited Prostate Cancer Risk
FOIU July 2018 The Role of genetic Testing for Inherited Prostate Cancer Risk Leonard G. Gomella, MD Chairman, Department of Urology Sidney Kimmel Cancer Center Thomas Jefferson University Philadelphia,
More informationThe Value of Panel Testing in Inherited Breast Cancer Risk Assessment. Rodney J. Scott Division of Molecular Medicine
The Value of Panel Testing in Inherited Breast Cancer Risk Assessment Rodney J. Scott Division of Molecular Medicine Mutation Detection Next Generation DNA sequencing has revolutionised mutation detection
More informationObjectives. Genetics in Cancer Treatment and Prevention. Genes
Objectives Genetics in Cancer Treatment and Prevention Cheryl LaFlore, ARNP, MSN, BC Understand how to integrate genetic and genomic information into oncology nursing practice Define the role of an oncology
More informationGenetic Testing for Familial Gastrointestinal Cancer Syndromes. C. Richard Boland, MD La Jolla, CA January 21, 2017
Genetic Testing for Familial Gastrointestinal Cancer Syndromes C. Richard Boland, MD La Jolla, CA January 21, 2017 Disclosure Information C. Richard Boland, MD I have no financial relationships to disclose.
More informationMyriad Financial Assistance Program (MFAP)
Myriad Financial Assistance Program (MFAP) MEDICAL CRITERIA Hereditary Cancer Products The Myriad Financial Assistance Program offers aid to patients who meet specific financial and medical requirements.
More informationGenetic testing for hereditary cancer
Genetic testing for hereditary cancer THE GENETICS OF HEREDITARY CANCER About half of all men and one-third of all women in the US will develop cancer during their lifetimes. Approximately 5% to 10% of
More information6/8/17. Genetics 101. Professor, College of Medicine. President & Chief Medical Officer. Hereditary Breast and Ovarian Cancer 2017
Genetics 101 Hereditary Breast and Ovarian Cancer 2017 Rebecca Sutphen, MD, FACMG Professor, College of Medicine President & Chief Medical Officer INVASIVE CANCER GENETICALLY ALTERED CELL HYPERPLASIA DYSPLASIA
More informationHereditary Prostate Cancer: From Gene Discovery to Clinical Implementation
Hereditary Prostate Cancer: From Gene Discovery to Clinical Implementation Kathleen A. Cooney, MD MACP Duke University School of Medicine Duke Cancer Institute (No disclosures to report) Overview Prostate
More informationGermline Multigene Panel Testing in Oncology: Genetic Counseling Perspective
Germline Multigene Panel Testing in Oncology: Genetic Counseling Perspective Sarah L. Campian, MS CGC Certified Genetic Counselor Nancy & James Grosfeld Cancer Genetics Center Objectives Identify patients/families
More informationGermline Genetic Testing for Breast Cancer Risk
Kathmandu, Bir Hospital visit, August 2018 Germline Genetic Testing for Breast Cancer Risk Evidence-based Genetic Screening Rodney J. Scott Demography in New South Wales (total population ~ 7,000,000)
More informationAre you at risk of Hereditary Cancer? Your Guide to the Answers
Are you at risk of Hereditary Cancer? Your Guide to the Answers What is Hereditary Cancer? The genes we are born with may contribute to our risk of developing certain types of cancer, including breast,
More informationPACGENE. A Research Project funded by the National Cancer Institute. Not for Patient Use (R01 CA 97075)
Not for Patient Use PACGENE A Research Project funded by the National Cancer Institute (R01 CA 97075) Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE Consortium) Tackling an important problem.
More informationPrevalence and clinical implications of BRCA1/2 germline mutations in Chinese women with breast cancer Yuntao Xie M.D., Ph.D.
Prevalence and clinical implications of BRCA1/2 germline mutations in Chinese women with breast cancer Yuntao Xie M.D., Ph.D. Hereditary Cancer Center, Peking University Cancer Hospital 1 Breast cancer
More informationDNA Genetic Cancer Risk Test. Test Report
Test Report CONTENTS SECTION 1 1-1. Customer Information 1-2. Test Report Summary 1-3. Test Report Details 1-4. List of Cancers / Tumors Tested SECTION 2 2-1. About the Test 2-2. References 1 CL0040-1_B
More informationThe lymphoma-associated NPM-ALK oncogene elicits a p16ink4a/prb-dependent tumor-suppressive pathway. Blood Jun 16;117(24):
DNA Sequencing Publications Standard Sequencing 1 Carro MS et al. DEK Expression is controlled by E2F and deregulated in diverse tumor types. Cell Cycle. 2006 Jun;5(11) 2 Lassandro L et al. The DNA sequence
More informationMSI positive MSI negative
Pritchard et al. 2014 Supplementary Figure 1 MSI positive MSI negative Hypermutated Median: 673 Average: 659.2 Non-Hypermutated Median: 37.5 Average: 43.6 Supplementary Figure 1: Somatic Mutation Burden
More informationInherited Cancer Genomics and Prevention:
Inherited Cancer Genomics and Prevention: How much cancer risk is inherited? Clinical utility of germline genetic testing in precision prevention and targeted therapy Kenneth Offit MD MPH Chief, Clinical
More informationSupplementary Table 1: Previous reports relevant to Early Onset Pancreatic Cancer (EOPC).
Supplementary Table 1: Previous reports relevant to Early Onset Pancreatic Cancer (EOPC). First author (year) Environmental and genetic factors Maximum age of EOPC group Number of EOPC cases Total number
More informationHereditary Cancer Products
Hereditary Products Integrated BRACAnalysis (BRCA1 and BRCA2 sequencing and large rearrangement testing (BART)), covered when: PERSONAL HISTORY of Breast (must meet at least 1) Diagnosed
More informationHereditary Breast and Ovarian Cancer Rebecca Sutphen, MD, FACMG
Hereditary Breast and Ovarian Cancer 2015 Rebecca Sutphen, MD, FACMG Among a consecutive series of 11,159 women requesting BRCA testing over one year, 3874 responded to a mailed survey. Most respondents
More informationBe Ready Pack Learn more about how Myriad myrisk is revolutionizing hereditary cancer testing.
Be Ready Pack Learn more about how Myriad myrisk is revolutionizing hereditary cancer testing. Hereditary cancer and you Approximately 5% to 10% of all cancers develop because a person inherited a genetic
More informationCASE STUDY. Germline Test for Mother and Follow up Testing for Daughter: Assessment of Hereditary Cancer Risk. Introduction.
CASE STUDY Germline Test for Mother and Follow up Testing for Daughter: Assessment of Hereditary Cancer Risk Introduction Germline cancer risk assessment tests are well-prescribed tests from Strand Life
More informationGEN ETICS AN D GEN OM ICS IN CANCER PREVENTION AN D TREATM EN T. Robert Nathan Slotnick MD PhD Director, Medical Genetics and Genomics
GEN ETICS AN D GEN OM ICS IN CANCER PREVENTION AN D TREATM EN T Robert Nathan Slotnick MD PhD Director, Medical Genetics and Genomics The Medical/Surgical/Radiation Oncologist s View of Genetics Cancer
More informationUnderstanding Your Positive Result. A guide to understanding your risk and taking action
Understanding Your Positive Result A guide to understanding your risk and taking action 2017 Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah 84108 PH: 1-800-469-7423 FX: 801-584-3615 1 PART
More informationpatient guide CancerNext genetic testing for hereditary cancer Because knowing your risk can mean early detection and prevention
patient guide CancerNext genetic testing for hereditary cancer Because knowing your risk can mean early detection and prevention Know the Basics Cancer occurs in about 1 in 3 adults in their lifetime types
More informationCASE STUDY. Germline Cancer Testing in A Proband: Extension of Benefits to Unaffected Family Members. Introduction. Patient Profile.
CASE STUDY Germline Cancer Testing in A Proband: Extension of Benefits to Unaffected Family Members Introduction Most cancers are caused by genetic damage resulting from random mutations and exposure to
More informationBreast and ovarian cancer risk assessment using multigene panel tests Prof Antonis Antoniou
Breast and ovarian cancer risk assessment using multigene panel tests Prof Antonis Antoniou Department of Public Health and Primary Care University of Cambridge, U.K. Cancer risk prediction in the era
More informationThe Role of Genetics in Ovarian Cancer Screening. Dawn DeLozier, Ph.D. Medical Geneticist, SAMC Associate Professor UCSF-Fresno
The Role of Genetics in Ovarian Cancer Screening Dawn DeLozier, Ph.D. Medical Geneticist, SAMC Associate Professor UCSF-Fresno How Much Breast and Ovarian Cancer Is Hereditary? 15%-20% 5%-10% Breast Cancer
More informationCASE STUDY. Mutation-Specific Testing: Eligibility for PARP Inhibitor Therapy Established. Introduction. Patient Profile.
CASE STUDY Mutation-Specific Testing: Eligibility for PARP Introduction Genetic testing is an emergent diagnostic technique that can provide specific and actionable inputs to the management of cancer therapy.
More informationGenetic Testing for BRCA1 and BRCA2 Genes
Genetic Testing for BRCA1 and BRCA2 Genes MP9478 Covered Service: Prior Authorization Required: Additional Information: Yes when meets criteria below Yes as shown below Pre and post-test genetic counseling
More informationPREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland
AWARD NUMBER: W81XWH-13-1-0421 TITLE: The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase III Clinical Trial in Ovarian Cancer PRINCIPAL INVESTIGATOR: Elizabeth
More informationMultiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer
www.impactjournals.com/oncotarget/ Oncotarget, Supplementary Materials 2016 Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer Supplementary Materials Supplementary
More informationRisk Factors and Early Detection Efforts for Pancreatic Cancer
HEADER SLIDE Risk Factors and Early Detection Efforts for Pancreatic Cancer by Jennifer B. Permuth, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer
More informationGenetic Testing For Ovarian Cancer: When, How And Who? Judith Balmaña, MD, PhD University Hospital Vall d Hebron Barcelona, Spain
Genetic Testing For Ovarian Cancer: When, How And Who? Judith Balmaña, MD, PhD University Hospital Vall d Hebron Barcelona, Spain Why Would We Consider Genetic Testing in Patients With Ovarian Cancer?
More informationGenetic Testing: who, what, why?
Genetic Testing: who, what, why? Gina Westhoff MD LMG Gynecologic Oncology March 16, 2019 Disclosures Speaker for Merck (unrelated to today s topic) Objectives Determine who should undergo genetic risk
More informationThe Genetics of Breast and Ovarian Cancer Prof. Piri L. Welcsh
The Genetics of Breast Piri L. Welcsh, PhD Research Assistant Professor University of Washington School of Medicine Division of Medical Genetics 1 Genetics of cancer All cancers arise from genetic and
More informationGenetic Cancer Susceptibility Panels Using Next Generation Sequencing
Genetic Cancer Susceptibility Panels Using Next Generation Sequencing Policy Number: 2.04.93 Last Review: 7/2017 Origination: 7/2013 Next Review: 7/2018 Policy Blue Cross and Blue Shield of Kansas City
More informationSurveillance of Individuals At High Risk For Developing Pancreatic Cancer
Surveillance of Individuals At High Risk For Developing Pancreatic Cancer Marco Bruno Erasmus Medical Center, Rotterdam Pancreatic Cancer Facts & figures One of the most fatal malignancies Overall 5-year
More informationClinical Cancer Genetics
Clinical Cancer Genetics Lisen Axell, MS, CGC University of Colorado Cancer Center Individuals with cancer Making surgical decisions (lump vs. mast) Making treatment decisions (XRT) Concerns for additional
More informationGenetic Determinants, Risk Assessment and Management
Genetic Determinants, Risk Assessment and Management Rachel Rando, MS, CGC Genetic Counselor Hunterdon Regional Cancer Center Flemington, NJ I have no disclosures. Acknowledgements: Staff of Hunterdon
More informationHereditary Cancer Update Strengthening Linkages Workshop April 22, 2017
Hereditary Cancer Update Strengthening Linkages Workshop April 22, 2017 Renée Perrier, MD MSc FRCPC Clinical Assistant Professor University of Calgary, Department of Medical Genetics Medical Director,
More informationCorporate Medical Policy
Corporate Medical Policy Moderate Penetrance Variants Associated with Breast Cancer in File Name: Origination: Last CAP Review: Next CAP Review: Last Review: moderate_penetrance_variants_associated_with_breast_cancer_
More informationCANCER GENETICS PROVIDER SURVEY
Dear Participant, Previously you agreed to participate in an evaluation of an education program we developed for primary care providers on the topic of cancer genetics. This is an IRB-approved, CDCfunded
More informationGenetic Testing for BRCA1 and BRCA2 Genes
Genetic Testing f BRCA1 and BRCA2 Genes MP9478 Covered Service: Pri Authization Required: Additional Infmation: Yes when meets criteria below Yes--as shown below Pre and post-test genetic counseling is
More informationGenetic Panel Testing and Implications for Cancer Care
Genetic Panel Testing and Implications for Cancer Care Dana Zakalik, M.D. Nancy and James Grosfeld Cancer Genetics Center Professor, OUWB Medical School MCC Board of Directors Meeting September 28, 2016
More informationPredisposition of Melanoma
Predisposition of Melanoma Nelleke Gruis Department of Dermatology Leiden University Medical Center The Netherlands OCTOBER 27TH 2017 Melanoma Risk Factors? Melanoma Predisposition 10% familial Manolio
More informationGenetic Testing Today: What Genes Can Tell Us. Living Beyond Breast Cancer Conference Kara N. Maxwell, MD, PhD University of Pennsylvania
Genetic Testing Today: What Genes Can Tell Us Living Beyond Breast Cancer Conference Kara N. Maxwell, MD, PhD University of Pennsylvania Overview of talk PART 1: Overview of Genetics PART 2: BRCA1/2 PART
More informationFamily Assessment. Objectives. Comprehensive Family History Important Inexpensive Underutilized genetic tool
Besides the BRCA genes, what else to consider in hereditary breast and ovarian cancer? Laurie M. Connors DNP, APNG, FNP-BC, AGN-BC Objectives Evaluate personal & family history to assess risk for hereditary
More informationGENETIC TESTING FOR HEREDITARY CANCER
UnitedHealthcare Oxford Clinical Policy GENETIC TESTING FOR HEREDITARY CANCER Policy Number: DIAGNOSTIC 004.27 T2 Effective Date: November 1, 2017 Table of Contents Page INSTRUCTIONS FOR USE... 1 CONDITIONS
More informationGenetics of Pancreatic Cancer. October 6, If you experience technical difficulty during the presentation:
Genetics of Pancreatic Cancer October 6, 2016 If you experience technical difficulty during the presentation: Contact WebEx Technical Support directly at: US Toll Free: 1-866-229-3239 Toll Only: 1-408-435-7088
More informationCorporate Medical Policy
Corporate Medical Policy Genetic Cancer Susceptibility Panels Using Next Generation File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_cancer_susceptibility_panels_using_next_generation_sequencing
More informationIdentification of patients suggestive of hereditary breast and ovarian cancer syndrome that warrants further professional evaluation.
Allina Breast Program Committee Consensus Guidelines These guidelines apply to clinical interventions that have well-documented outcomes, but whose outcomes are not clearly desirable to all patients Identification
More informationProactive Patient Paves the Way for Genetic Testing of Eight Family Members
CASE STUDY Proactive Patient Paves the Way for Genetic Testing of Eight Family Members Quick Summary Samar Mohite * was diagnosed with colon adenocarcinoma at the age of 49 years. Genetic counselling was
More informationACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes
ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes Sapna Syngal, MD, MPH, FACG, 1,2,3 Randall E. Brand, MD, FACG, 4 James M. Church, MD, FACG, 5,6,7
More informationGenetic Risk Assessment for Cancer
Genetic Risk Assessment for Cancer Jennifer Siettmann, MS CGC Certified Genetic Counselor Banner MD Anderson Cancer Center Objectives Describe the role of genetic counseling and genetic testing in patient
More informationPanel Testing and SNP Testing (Polygenic Risk Score) in Asian Women Soo Teo PhD FASc Head of Breast Cancer Research Programme Cancer Research
Panel Testing and SNP Testing (Polygenic Risk Score) in Asian Women Soo Teo PhD FASc Head of Breast Cancer Research Programme Cancer Research Malaysia E mail: soohwang.teo@cancerresearch.my How much of
More informationPredictive and Diagnostic Testing for Cancer in Women. Aparna Rajadhyaksha MD
Predictive and Diagnostic Testing for Cancer in Women Aparna Rajadhyaksha MD Hereditary Cancer s in Women BRCA1 &2 Other Breast Cancer Genes Li Fraumeni PTEN CHEK2 BRCA1&2 t BRCA1 is part of a complex
More informationA pathogenic mutation was identified in the BRCA1 gene.
Hereditary Cancer Risk Test ORDERING PHYSICIAN Dr. Jenny Jones Sample Medical Group 123 Main St. Sample, CA SPECIMEN Type: Saliva Barcode: 223 234234 2343 Collected: Apr 13, 2016 Received: Apr 14, 2016
More informationHEREDITY & CANCER: Breast cancer as a model
HEREDITY & CANCER: Breast cancer as a model Pierre O. Chappuis, MD Divisions of Oncology and Medical Genetics University Hospitals of Geneva, Switzerland Genetics, Cancer and Heredity Cancers are genetic
More informationManagement of BRCA Positive Breast Cancer. Archana Ganaraj, MD February 17, 2018 UPDATE ON WOMEN S HEALTH
Management of BRCA Positive Breast Cancer Archana Ganaraj, MD February 17, 2018 UPDATE ON WOMEN S HEALTH The number of American women who have lost their lives to breast cancer outstrips the total number
More informationCOLON CANCER & GENETICS VERMONT COLORECTAL CANCER SUMMIT NOVEMBER 15, 2014
COLON CANCER & GENETICS VERMONT COLORECTAL CANCER SUMMIT NOVEMBER 15, 2014 WENDY MCKINNON, MS, CGC CERTIFIED GENETIC COUNSELOR FAMILIAL CANCER PROGRAM UNIVERSIT Y OF VERMONT MEDICAL CENTER 1 CHARACTERISTICS
More informationpatient guide CancerNext-Expanded genetic testing for hereditary cancer Because knowing your risk can mean early detection and prevention
patient guide CancerNext-Expanded genetic testing for hereditary cancer Because knowing your risk can mean early detection and prevention Know the Basics Cancer occurs in about 1 in 3 adults in their lifetime
More informationOvaNext. patient guide. genetic testing for hereditary breast, ovarian, and uterine cancer
patient guide OvaNext genetic testing for hereditary breast, ovarian, and uterine cancer Because knowing your risk can mean early detection and prevention About half of the women diagnosed with uterine
More informationMEDICAL POLICY Genetic Testing for Breast and Ovarian Cancers
POLICY: PG0067 ORIGINAL EFFECTIVE: 07/30/02 LAST REVIEW: 01/25/18 MEDICAL POLICY Genetic Testing for Breast and Ovarian Cancers GUIDELINES This policy does not certify benefits or authorization of benefits,
More informationGenetic Risk Assessment for Cancer
Genetic Risk Assessment for Cancer Jennifer Siettmann, MS CGC Certified Genetic Counselor/Cancer Risk Counselor Banner Good Samaritan Cancer Screening & Prevention Program Objectives Describe the role
More informationRisk of Colorectal Cancer (CRC) Hereditary Syndromes in GI Cancer GENETIC MALPRACTICE
Identifying the Patient at Risk for an Inherited Syndrome Sapna Syngal, MD, MPH, FACG Director, Gastroenterology Director, Familial GI Program Dana-Farber/Brigham and Women s Cancer Center Associate Professor
More informationMedical Policy Manual. Topic: Genetic Testing for Hereditary Breast and/or Ovarian Cancer. Date of Origin: January 27, 2011
Medical Policy Manual Topic: Genetic Testing for Hereditary Breast and/or Ovarian Cancer Date of Origin: January 27, 2011 Section: Genetic Testing Last Reviewed Date: July 2014 Policy No: 02 Effective
More informationAssessing Your Patient s Breast Cancer Risk: Is Genetic Testing Necessary?
May 16, 2016 Assessing Your Patient s Breast Cancer Risk: Is Genetic Testing Necessary? Presenter: Emily Kuchinsky, MS, CGC 1 Experiences with Genetic Testing Adverse Events in Cancer Genetic Testing:
More informationSchedule of Accreditation issued by United Kingdom Accreditation Service 2 Pine Trees, Chertsey Lane, Staines-upon-Thames, TW18 3HR, UK
2 Pine Trees, Chertsey Lane, Staines-upon-Thames, TW18 3HR, UK NW Thames Regional Genetics Laboratory Northwick Park Hospital Watford Road Harrow HA1 3UJ United Kingdom Contact: Caroline Sullivan Tel:
More informationNGS for Cancer Predisposition
NGS for Cancer Predisposition Colin Pritchard MD, PhD University of Washington Dept. of Lab Medicine AMP Companion Society Meeting USCAP Boston March 22, 2015 Disclosures I am an employee of the University
More informationPALB2 mutations in European familial pancreatic cancer families
Clin Genet 2010: 78: 490 494 Printed in Singapore. All rights reserved Short Report 2010 John Wiley & Sons A/S CLINICAL GENETICS doi: 10.1111/j.1399-0004.2010.01425.x PALB2 mutations in European familial
More informationEvaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes
Evaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes Melinda S. Yates, PhD Department of Gynecologic Oncology & Reproductive Medicine University
More information10/21/ New Release, Quest Diagnostics Nichols Institute, Valencia
NEW TESTS Please Note: Not all test codes assigned to each assay are listed in the table of contents. Please refer to the complete listing on the page numbers indicated. Test Code Test Name Effective Date
More informationPopulations Interventions Comparators Outcomes Individuals: With a personal and/or family history suggesting an inherited cancer syndrome
Genetic Cancer Susceptibility Panels Using Next- Generation (20493) Medical Benefit Effective Date: 01/01/18 Next Review Date: 09/18 Preauthorization No Review Dates: 09/13, 09/14, 09/15, 09/16, 09/17
More informationP NK. Breast Cancer Genetic Risk Test. Test Report
Test Report CONTENTS SECTION 1 1-1. Patient Information 1-2. Test Report Summary 1-3. Test Report Details 1-4. List of Genes Tested SECTION 2 2-1. About the Test 2-2. References 1-1. Patient Information
More informationModerate Penetrance Variants Associated With Breast Cancer in Individuals at High Breast Cancer Risk
Moderate Penetrance Variants Associated With Breast Cancer in Individuals at High Breast Cancer Risk Policy Number: 2.04.126 Last Review: 3/2018 Origination: 3/2017 Next Review: 3/2019 Policy Blue Cross
More informationHereditary Cancer Risk Assessment for Gynecological Cancers. FarrNezhatMD.com
Hereditary Cancer Risk Assessment for Gynecological Cancers FarrNezhatMD.com Image credit: PLOS blogs 5-10% hereditary 10-20% 70-80% sporadic Genetic Changes and Cancer Cancer begins with a genetic
More information