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

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.

On new reproductive technologies and family ethics: pre-implantation genetic diagnosis for sibling donor in Israel and Germany.

This paper discusses the policy debate and ethical discussion surrounding pre-implantation genetic diagnosis (PGD) for sibling donor (SD) in Germany and Israel. Based on an analysis of the regulations and ethical discourse concerning a unique form of new reproductive technology (NRT)--PGD for SD--we complement the scholarly discussion of NRTs in these countries, by pointing to an explanatory factor that has been so far neglected, namely the hegemonic notions regarding the ideal relationship between the generations, and the mutual obligations between different family members in Germany and Israel. We argue the fact that PGD (in general) and PGD for SD (in particular) have been banned in Germany, but were endorsed without hesitation in Israel, has to do with different perceptions of family ethics within the two societies. Furthermore, we argue that this factor contributes significantly to the more general understanding of German and Israeli policies regarding NRTs.