Gene Panel Testing for Inherited Cancer Risk

2014 ◽  
Vol 12 (9) ◽  
pp. 1339-1346 ◽  
Author(s):  
Michael J. Hall ◽  
Andrea D. Forman ◽  
Robert Pilarski ◽  
Georgia Wiesner ◽  
Veda N. Giri
Keyword(s):  
Cancer Risk ◽  
Gene Panel ◽  
Inherited Cancer ◽  
Panel Testing ◽  
Gene Panel Testing

scholarly journals Germline variants and phenotypic spectrum in a Canadian cohort of individuals with diffuse gastric cancer

2019 ◽  
Vol 27 (2) ◽  
Author(s):  
M. Aronson ◽  
C. Swallow ◽  
A. Govindarajan ◽  
K. Semotiuk ◽  
Z. Cohen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Detection Rate ◽  
Gene Panel ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
Detection Rates ◽  
Inherited Cancer ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing

Background CDH1 pathogenic variants (PV) cause the majority of inherited diffuse-gastric cancer (DGC), but have low detection rates and vary geographically. This study examines hereditary causes of DGC in patients from Ontario, Canada. Methods Eligible DGC cases at the Zane Cohen Centre (ZCC) underwent multi-gene panel or CDH1 single-site testing if they met 2015 International Gastric Cancer Linkage Consortium (IGCLC) criteria, isolated DGC <50 or family history suggestive of an inherited cancer syndrome. A secondary aim was to review all CDH1 families at the ZCC to assess cancer penetrance. Results 85 DGC patients underwent CDH1 (n=43) or multi-gene panel testing (n=42), and 15 (17.6%) PV or likely PV were identified.  CDH1 detection rate was 9.4% (n=8/85), and 11% (n=7/65) using IGCLC criteria.  No CDH1 PV identified in isolated DGC <40, but one PV identified in isolated DGC<50.  Multi-gene panel from 42 individuals identified 9 PV (21.4%) including CDH1, STK11, ATM, BRCA2, MLH1 and MSH2.  Review of 81 CDH1 carriers revealed that 10% had DGC (median age:48, range:38-59), 41% were unaffected (median age:53, range:26-89).  Three families had lobular-breast cancer (LBC) only.  Non-DGC/LBC malignancies included colorectal, gynecological, kidney/bladder, prostate, testicular and ductal breast. Conclusions Low detection rate of CDH1 in Ontario DGC patients.  No CDH1 PV found in isolated DGC <40, but identified in isolated DGC<50. Multi-gene panels are recommended for all DGC under age 50, and those meeting the IGCLC criteria, given overlapping phenotype with other hereditary conditions. HDGC phenotype is evolving with a spectrum of non-DGC/LBC cancers.

Abstract P2-09-06: Multi-gene panel testing for hereditary cancer risk

2016 ◽  
Author(s):  
S Yadav ◽  
R Ladkany ◽  
J Fulbright ◽  
H Dreyfuss ◽  
A Reeves ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Hereditary Cancer ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Panel Testing

Clinical impact of multi-gene panel testing for hereditary breast and ovarian cancer risk assessment.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1513-1513
Author(s):  
Leif W. Ellisen ◽  
Allison W. Kurian ◽  
Andrea J Desmond ◽  
Meredith Mills ◽  
Stephen E Lincoln ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Assessment ◽  
Cancer Risk ◽  
Clinical Impact ◽  
Gene Panel ◽  
Cancer Risk Assessment ◽  
Ovarian Cancer Risk ◽  
Breast And Ovarian Cancer ◽  
Panel Testing ◽  
Gene Panel Testing

Expanded yield of multiplex panel testing in fully accrued prospective trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1525-1525
Author(s):  
Gregory Idos ◽  
Allison W. Kurian ◽  
Charite Nicolette Ricker ◽  
Duveen Sturgeon ◽  
Julie Culver ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Clinical Utility ◽  
Diagnostic Yield ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Cancer Risk Assessment ◽  
Panel Testing ◽  
Gene Panel Testing

1525 Background: Genetic testing is a powerful tool for stratifying cancer risk. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. However, the diagnostic yield and clinical utility of panels remain to be further delineated. Methods: A report of a fully accrued trial (N = 2000) of patients undergoing cancer-risk assessment. Patients were enrolled in a multicenter prospective cohort study where diagnostic yield and off-target mutation detection was evaluated of a 25 gene MGP comprised of APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were enrolled if they met standard testing guidelines or were predicted to have a ≥2.5% mutation probability by validated models. Differential diagnoses (DDx) were generated after expert clinical genetics assessment, formulating up to 8 inherited cancer syndromes ranked by estimated likelihood. Results: 1998/2000 patients had reported MGP test results. Women constituted 81% of the sample, and 40% were Hispanic; 241 tested positive for at least 1 pathogenic mutation (12.1%) and 689 (34.5%) patients carried at least 1 variant of uncertain significance. The most frequently identified mutations were in BRCA1 (17%, n = 41), BRCA2 (15%, n = 36), APC (8%, n = 19), CHEK2 (7%, n = 17), ATM (7%, n = 16). 39 patients (16%) had at least 1 pathogenic mutation in a mismatch repair (MMR) gene ( MLH1, n = 10; MSH2, n = 10; MSH6, n = 8; PMS2, n = 11). 43 individuals (18%) had MUTYH mutations – 41 were monoallelic. Among 19 patients who had mutations in APC – 16 were APC I1307K. Only 65% (n = 159) of PV results were included in the DDx, with 35% (n = 86) of mutations not clinically suspected. Conclusions: In a diverse cohort, multiplex panel use increased genetic testing yield substantially: 35% carried pathogenic mutations in unsuspected genes, suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment. The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations. Follow-up is ongoing to assess the clinical utility of multiplex gene panel testing. Clinical trial information: NCT02324062.

BRIDGES, Breast Cancer Risk after Diagnostic Gene Sequencing, HORIZON2020

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 12-15
Author(s):  
Peter Devilee ◽  
Marjanka Schmidt
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Gene Panel ◽  
Prophylactic Surgery ◽  
Panel Testing ◽  
Cancer Susceptibility Genes ◽  
Risk Estimates ◽  
Gene Panel Testing

"Breast cancer affects more than 360,000 women per year in the EU and causes more than 90,000 deaths. Identification of women at high risk of the disease can lead to early detection or disease prevention through intensive screening, therapeutic and/or lifestyle preventive measures, or prophylactic surgery. Breast cancer risk is determined by a combination of genetic and lifestyle risk factors. The advent of next generation sequencing has opened the opportunity for testing in many disease genes, and diagnostic gene panel testing is being introduced in many EU countries. However, the cancer risks associated with most variants in most genes are unknown. This leads to a major problem in appropriate counselling and management of women undergoing panel testing. The BRIDGES and B-CAST projects are jointly building a knowledge base that will allow identification of women at high-risk of specific subtypes of breast cancer, through comprehensive evaluation of DNA variants in known and suspected breast cancer genes. The effort exploits the huge resources established through the Breast Cancer Association Consortium (BCAC) and ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles). Existing datasets will be expanded by sequencing all known breast cancer susceptibility genes in >100,000 breast cancer cases and controls from population-based studies. Risk factor and tumour genome data have been collected for 10,000 cases. Jointly, the data will allow us to generate a comprehensive risk model with unprecedented discriminative power, that can provide personalised risk estimates. We will develop online tools to aid the interpretation of gene variants and provide risk estimates in a user-friendly format, to help genetic counsellors and patients worldwide to make informed clinical decisions for risk management. We will evaluate the acceptability and utility of comprehensive gene panel testing in the clinical genetics context."

scholarly journals Multi-Gene Panel Testing in Gastroenterology: Are We Ready for the Results?

2021 ◽  
pp. 1-7
Author(s):  
Flávio Pereira ◽  
Manuel R. Teixeira ◽  
Mário Dinis Ribeiro ◽  
Catarina Brandão
Keyword(s):  
Genetic Testing ◽  
Cancer Susceptibility ◽  
Familial Cancer ◽  
Short Review ◽  
Gene Panel ◽  
Inherited Cancer ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Patients At Risk ◽  
Familial Cancer Risk

Genetic testing aims to identify patients at risk for inherited cancer susceptibility. In the last decade, there was a significant increase in the request of broader panels of genes as multi-gene panel testing became widely available. However, physicians may be faced with genetic findings for which there is lack of management evidence, despite some progress in understanding their clinical relevance. In this short review, we discuss the advantages and the drawbacks related to multi-gene panel testing in the setting of a Gastrointestinal Familial Cancer Risk clinic. We also summarize the available recommendations on management of pathogenic variant carriers.

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