Abstract

Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1/BRCA2. We employed an online survey of 65 questions covering four areas: laboratory characteristics, details on technological methods, variant classification, and client-support information. Eight United States (US) laboratories and 78 non-US laboratories completed the survey. Most laboratories (93%; 80/86) used MPS platforms to identify variants. Laboratories differed widely on: (1) technologies used for large rearrangement detection; (2) criteria for minimum read depths; (3) non-coding regions sequenced; (4) variant classification criteria and approaches; (5) testing volume ranging from 2 to 2.5 × 105 tests annually; and (6) deposition of variants into public databases. These data may be useful for national and international agencies to set recommendations for quality standards for BRCA1/BRCA2 clinical testing. These standards could also be applied to testing of other disease genes.

Details

Title
Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices
Author
Amanda Ewart Toland 1   VIAFID ORCID Logo  ; Forman, Andrea 2 ; Couch, Fergus J 3 ; Culver, Julie O 4 ; Eccles, Diana M 5 ; Foulkes, William D 6   VIAFID ORCID Logo  ; Hogervorst, Frans B L 7 ; Houdayer, Claude 8 ; Levy-Lahad, Ephrat 9 ; Monteiro, Alvaro N 10   VIAFID ORCID Logo  ; Neuhausen, Susan L 11 ; Plon, Sharon E 12 ; Sharan, Shyam K 13 ; Spurdle, Amanda B 14 ; Szabo, Csilla 15 ; Brody, Lawrence C 15 

 Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA 
 Fox Chase Cancer Center, Philadelphia, PA, USA 
 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA 
 USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA 
 Faculty of Medicine, University of Southampton, Southampton, UK 
 Departments of Human Genetics, Medicine and Oncology, McGill University, Montreal, QC, Canada 
 Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, Netherlands 
 Oncogenetics and INSERM U830, Institut Curie, Paris and Paris Descartes University, Paris, France 
 Faculty of Medicine, Shaare Zedek Medical Center, Hebrew University of Jerusalem and Medical Genetics Institute, Jerusalem, Israel 
10  Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA 
11  Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA 
12  Baylor College of Medicine, Houston, TX, USA 
13  Mouse Cancer Genetics Program, Center for Cancer Biology, National Cancer Institute, National Institutes of Health, Frederick, MD, USA 
14  Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia 
15  National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA 
Pages
1-8
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20567944
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2002473253
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.