Inbal Barnes-Kedar1, Rinat Bernstein-Molho2,3, Nava Ginzach1, Shulamit Hartmajer4, Tamar Shapira5, Nurit Magal1, Marina Lifshitc Kalis1, Tamar Peretz6, Mordechai Shohat5, Lina Basel-Salmon1,7, Eitan Friedman7,3, Lily Bazak1, Yael Goldberg8,9. 1. Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel. 2. Breast Cancer Center, Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 3. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 4. Medical Genetics Institute, Meir Medical Center, Kfar Sava, Israel. 5. Maccabi Health Services, Rehovot, Israel. 6. Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. 7. Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 8. Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel. yaelgo43@gmail.com. 9. Maccabi Health Services, Rehovot, Israel. yaelgo43@gmail.com.
Abstract
PURPOSE: BRCA1 and BRCA2 genotyping results have clinical implications for cancer risk assessment and targeted therapy. Current practice in Israel is to genotype for the predominant BRCA1/2 mutations first, followed by full gene analysis in eligible mutation-negative individuals. This work assessed the rate of non-predominant mutations in BRCA1/2 in ethnically diverse high-risk cases. METHODS: Breast and/or ovarian cancer patients who tested negative for the predominant BRCA1/2 mutations were referred for comprehensive BRCA1/2 genotyping if calculated risk for carrying a BRCA mutation was ≥ 10%. RESULTS: Of 1258 eligible patients, 41 (3.3%) carried one of 38 mutations: 3% of Ashkenazi Jews and 3.4% of mixed ethnicities. Detection rate was < 5% among patients diagnosed with cancer younger than 40 or with bilateral breast cancer, and was 5.5% of ovarian cancer patients. Three of the carriers (7.3%) carried gene rearrangements. Three mutations were reported in more than one case. CONCLUSIONS: The overall yield of comprehensive BRCA1/2 testing in ethnically diverse high-risk Israeli individuals is 3.3%. This is lower than expected by probability models. A slightly higher rate of BRCA1/2 carriers was seen among ovarian cancer cases. These data should guide BRCA1/2 optimal testing strategy in Israel.
PURPOSE:BRCA1 and BRCA2 genotyping results have clinical implications for cancer risk assessment and targeted therapy. Current practice in Israel is to genotype for the predominant BRCA1/2 mutations first, followed by full gene analysis in eligible mutation-negative individuals. This work assessed the rate of non-predominant mutations in BRCA1/2 in ethnically diverse high-risk cases. METHODS: Breast and/or ovarian cancerpatients who tested negative for the predominant BRCA1/2 mutations were referred for comprehensive BRCA1/2 genotyping if calculated risk for carrying a BRCA mutation was ≥ 10%. RESULTS: Of 1258 eligible patients, 41 (3.3%) carried one of 38 mutations: 3% of Ashkenazi Jews and 3.4% of mixed ethnicities. Detection rate was < 5% among patients diagnosed with cancer younger than 40 or with bilateral breast cancer, and was 5.5% of ovarian cancerpatients. Three of the carriers (7.3%) carried gene rearrangements. Three mutations were reported in more than one case. CONCLUSIONS: The overall yield of comprehensive BRCA1/2 testing in ethnically diverse high-risk Israeli individuals is 3.3%. This is lower than expected by probability models. A slightly higher rate of BRCA1/2 carriers was seen among ovarian cancer cases. These data should guide BRCA1/2 optimal testing strategy in Israel.
Entities:
Keywords:
Ashkenazi; BRCA1 BRCA2; Breast cancer; Founder; Israel; Jewish; Non-founder mutations; Ovarian cancer
Authors: G A Yanus; E L Savonevich; A P Sokolenko; A A Romanko; V I Ni; E Kh Bakaeva; O A Gorustovich; I V Bizin; E N Imyanitov Journal: Fam Cancer Date: 2022-05-21 Impact factor: 2.375
Authors: Christina N Cordeiro Mitchell; Bailey McGuinness; Eliana Fine; William G Kearns; Mindy S Christianson; James Segars; Lisa M Pastore Journal: J Assist Reprod Genet Date: 2020-03-24 Impact factor: 3.412
Authors: S Lieberman; R Chen-Shtoyerman; Z Levi; S Shkedi-Rafid; S Zuckerman; R Bernstein-Molho; G Reznick Levi; S S Shachar; A Flugelman; V Libman; I Kedar; S Naftaly-Nathan; I Lagovsky; T Peretz; N Karminsky; S Carmi; E Levy-Lahad; Y Goldberg Journal: Breast Cancer Res Treat Date: 2022-03-12 Impact factor: 4.624