دورية أكاديمية
The Diagnostic Yield and Implications of Targeted Founder Pathogenic Variant Testing in an Israeli Cohort
| العنوان: | The Diagnostic Yield and Implications of Targeted Founder Pathogenic Variant Testing in an Israeli Cohort |
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| المؤلفون: | Aasem Abu Shtaya, Inbal Kedar, Samar Mattar, Ahmad Mahamid, Lina Basel-Salmon, Sarit Farage Barhom, Sofia Naftaly Nathan, Nurit Magal, Noy Azulay, Michal Levy Zalcberg, Rakefet Chen-Shtoyerman, Ori Segol, Mor Seri, Gili Reznick Levi, Shiri Shkedi-Rafid, Chana Vinkler, Iris Netzer, Ofir Hagari Bechar, Liat Chamma, Sari Liberman, Yael Goldberg |
| المصدر: | Cancers, Vol 16, Iss 1, p 94 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | BRCA1, BRCA2, Lynch, APC, cancer, founder, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020–January 2023. Those with a known familial PV (n = 370) were excluded from the analysis. Among the remainder, 128/1758 (7%) were heterozygous for at least one variant, and 44 (34%) carried a PV of medium-high penetrance (MHPV). Cancer was diagnosed in 1519/1758 patients (86%). The diagnostic yield of founder MHPV testing was 2% in cancer patients and 4% in healthy individuals with a positive family history. It was higher in Ashkenazi Jews than non-Ashkenazi Jews and Arabs, but not over 10% for any type of cancer, and it was significantly higher in younger (50 years) individuals (7% vs. 1%). Eighty-four of the heterozygotes (66%), mostly Ashkenazi Jews, harbored a low-penetrance variant (LPV) not associated with the diagnosed cancer, usually APC c.3902T>A. These findings question the advantage of two-step testing. LPVs should not be included in targeted testing because this can lead to an overestimation of the yield, and their detection does not preclude further comprehensive testing. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 16010094 2072-6694 |
| العلاقة: | https://www.mdpi.com/2072-6694/16/1/94Test; https://doaj.org/toc/2072-6694Test |
| DOI: | 10.3390/cancers16010094 |
| الوصول الحر: | https://doaj.org/article/7d651f27b0f8464d983bdf8d3c7b5bd4Test |
| رقم الانضمام: | edsdoj.7d651f27b0f8464d983bdf8d3c7b5bd4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 16010094 20726694 |
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| DOI: | 10.3390/cancers16010094 |