Outcomes of multigene panel testing for hereditary cancer in two Israeli medical centers 2013-2024
Yael Laitman1, Shelley Zalmanoviz2, Iris Netzer2
1Oncogenetics Unit, Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Oncogenetics Service, Assuta Medical Center, Ramat Hachayal, Tel Aviv, Israel.
Purpose:
Multigene panel testing (MGPT) enables simultaneous detection of germline pathogenic/likely pathogenic variants (P/LP SV) in cancer susceptibility genes (CSG). The utility of MGPT in Israel, where most individuals eligible for oncogenetic testing undergo first-pass genotyping for predominant PSVs in the BRCA1, BRCA2, MSH2, and MSH6 genes, has not been reported.
Methods:
Individuals who underwent MGPT after oncogenetic counseling between October 2013 and December 2024 were eligible for participation in this ethically approved study. NGS genotyping of 29-160 genes was performed using commercial or in-house platforms. Clinical data were obtained from records.
Results:
Among 2990 individuals, 139 pathogenic sequence variants were detected in 39 genes in 234 individuals (7.8%). Recurring PSVs in BRCA1, BRCA2, CHEK2, ATM, MSH2, and MSH6 were noted. CHEK2 (c.592+3A>T), PMS2 (c.943C>T), and CDKN2A (c.176T>G) were identified as potentially recurring founder variants.
Conclusions:
The yield of MGPT in Israel, after exclusion of predominant founder PSVs, was modest. The identification of recurring PSVs warrants further investigation and potential inclusion in updated first-pass genotyping schemes.
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