TY - JOUR
T1 - Diagnostic yield of multigene panel testing in an Israeli cohort
T2 - enrichment of low-penetrance variants
AU - Bernstein-Molho, Rinat
AU - Friedman, Eitan
AU - Kedar, Inbal
AU - Laitman, Yael
AU - Allweis, Tanir M.
AU - Gal-Yam, Einav Nili
AU - Feldman, Hagit Baris
AU - Grinshpun, Albert
AU - Halpern, Naama
AU - Hartmajer, Shulamit
AU - Kadouri, Luna
AU - Katz, Lior H.
AU - Kaufman, Bella
AU - Laish, Ido
AU - Levanon, Keren
AU - Philipsborn, Shira Litz
AU - Ludman, Mark
AU - Moran, Gal
AU - Peretz, Tamar
AU - Reinstein, Eyal
AU - Levi, Gili Reznick
AU - Safra, Tamar
AU - Shkedi, Shiri
AU - Vinkler, Chana
AU - Levy, Zohar
AU - Goldberg, Yael
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Cancer predisposition
KW - Clinical utility
KW - Inherited cancer syndromes
KW - Low-penetrance variants
KW - Multi-gene panel testing
KW - Recurrent mutations
UR - http://www.scopus.com/inward/record.url?scp=85083578983&partnerID=8YFLogxK
U2 - 10.1007/s10549-020-05633-2
DO - 10.1007/s10549-020-05633-2
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C2 - 32303989
AN - SCOPUS:85083578983
SN - 0167-6806
VL - 181
SP - 445
EP - 453
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -
