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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2020

01-06-2020 | Breast Cancer | Epidemiology

Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants

Authors: Rinat Bernstein-Molho, Eitan Friedman, Inbal Kedar, Yael Laitman, Tanir M. Allweis, Einav Nili Gal-Yam, Hagit Baris Feldman, Albert Grinshpun, Naama Halpern, Shulamit Hartmajer, Luna Kadouri, Lior H. Katz, Bella Kaufman, Ido Laish, Keren Levanon, Shira Litz Philipsborn, Mark Ludman, Gal Moran, Tamar Peretz, Eyal Reinstein, Gili Reznick Levi, Tamar Safra, Shiri Shkedi, Chana Vinkler, Zohar Levy, Yael Goldberg

Published in: Breast Cancer Research and Treatment | Issue 2/2020

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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.

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.

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.

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.
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Metadata
Title
Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants
Authors
Rinat Bernstein-Molho
Eitan Friedman
Inbal Kedar
Yael Laitman
Tanir M. Allweis
Einav Nili Gal-Yam
Hagit Baris Feldman
Albert Grinshpun
Naama Halpern
Shulamit Hartmajer
Luna Kadouri
Lior H. Katz
Bella Kaufman
Ido Laish
Keren Levanon
Shira Litz Philipsborn
Mark Ludman
Gal Moran
Tamar Peretz
Eyal Reinstein
Gili Reznick Levi
Tamar Safra
Shiri Shkedi
Chana Vinkler
Zohar Levy
Yael Goldberg
Publication date
01-06-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05633-2

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