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Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants.
- Source :
-
Breast cancer research and treatment [Breast Cancer Res Treat] 2020 Jun; Vol. 181 (2), pp. 445-453. Date of Electronic Publication: 2020 Apr 18. - Publication Year :
- 2020
-
Abstract
- Background: Carriers of pathogenic variants (PVs) in moderate-high-penetrance cancer susceptibility genes are offered tailored surveillance schemes for early cancer diagnosis. The clinical implications of low-penetrance variant carriers are less clear.<br />Methods: Clinical and demographic data were retrieved for a cohort of Israeli individuals who underwent oncogenetic testing by the 30-gene cancer panel at Color Genomics laboratory, between 04/2013 and 12/2018.<br />Results: Of 758 genotyped individuals, 504 had been diagnosed with cancer prior to testing: 283 (56%) had breast cancer and 106 (21%) colorectal cancer. Pathogenic or likely pathogenic (P/LP) variants were detected in 123 (16%) individuals. Overall, 44 different P/LP variants were detected in 18/30 cancer susceptibility genes; 20 of them were founder/recurrent mutations. Of the carriers, 39 (32%), 10 (8%), and 74 (60%) carried high-, moderate-, or low-penetrance variants, respectively. After excluding low-penetrance variants, 7% (33/504) of all cancer patients, 6% of breast or ovarian cancer patients were found to be carriers, as well as 7% (14/203) of individuals with colonic polyps, and 4% (11/254) of cancer-free individuals.<br />Conclusions: The diagnostic yield of moderate- and high-penetrance PVs using multigene panel testing was 6%, with 3.7% carriers of non-recurrent PVs. This yield should be discussed during pre-test counseling, and emphasizes the need for harmonized recommendations regarding clinical implications of low-penetrance variants.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Breast Neoplasms epidemiology
Breast Neoplasms genetics
Cohort Studies
Ethnicity statistics & numerical data
Female
Follow-Up Studies
Humans
Israel epidemiology
Middle Aged
Penetrance
Prognosis
Young Adult
Biomarkers, Tumor genetics
Breast Neoplasms diagnosis
Early Detection of Cancer methods
Ethnicity genetics
Genetic Predisposition to Disease
Genetic Testing methods
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7217
- Volume :
- 181
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Breast cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 32303989
- Full Text :
- https://doi.org/10.1007/s10549-020-05633-2