Rinat Bernstein-Molho1,2, Yael Laitman3, Hagit Schayek3, Orit Reish4,2, Shira Lotan4, Sara Haim4, Jamal Zidan5,6, Eitan Friedman7,8. 1. Breast Cancer Center, Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Ramat Gan, Israel. 2. Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. 3. Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Ramat Gan, Israel. 4. Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel. 5. The Oncology Division, Ziv Medical Center, Safed, Israel. 6. Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel. 7. Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Ramat Gan, Israel. eitan.friedman@sheba.health.gov.il. 8. Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. eitan.friedman@sheba.health.gov.il.
Abstract
BACKGROUND: Hereditary breast cancer is predominantly associated with germline mutations in the BRCA1 or BRCA2 genes. A few recurring mutations in these genes were reported in ethnically diverse Jewish populations. Since 2013, most oncogenetic laboratories in Israel adopted a two-step approach for BRCA1/2 genotyping, where the first step is genotyping for 14 seemingly recurring mutations-first-pass genotyping. The aim of this study was to assess the yield of this targeted BRCA sequencing. METHODS: Clinical and genotyping data of all individuals who underwent oncogenetic counseling and first-pass BRCA genotyping at the Oncogenetic Service Sheba and Assaf Harofeh Medical Centers from 1 February 2013 to 30 June 2017 were reviewed. All study participants were unrelated to each other. RESULTS: Overall, 5152 oncogenetic tests were reviewed in the present study, of which 4452 had no a priori known familial mutation. The majority of participants (68.6%) were genotyped because of personal history of cancer; 20.6% were tested because of family history of cancer, and details for the remaining 10.7% were missing. Overall, 256/4452 (5.8%) carriers were detected, 141 BRCA1 and 115 BRCA2 mutation carriers. In 54% of cancer-free carriers, no clinically suspicious family history of cancer was ascertained. CONCLUSIONS: The currently used scheme of first-pass genotyping in Israel seems to have a high yield of mutation detection even in the absence of a significant family history of cancer. The challenge is to optimize the currently used targeted panel of common mutations and adjust it to the accumulating new data in the Israeli population.
BACKGROUND: Hereditary breast cancer is predominantly associated with germline mutations in the BRCA1 or BRCA2 genes. A few recurring mutations in these genes were reported in ethnically diverse Jewish populations. Since 2013, most oncogenetic laboratories in Israel adopted a two-step approach for BRCA1/2 genotyping, where the first step is genotyping for 14 seemingly recurring mutations-first-pass genotyping. The aim of this study was to assess the yield of this targeted BRCA sequencing. METHODS: Clinical and genotyping data of all individuals who underwent oncogenetic counseling and first-pass BRCA genotyping at the Oncogenetic Service Sheba and Assaf Harofeh Medical Centers from 1 February 2013 to 30 June 2017 were reviewed. All study participants were unrelated to each other. RESULTS: Overall, 5152 oncogenetic tests were reviewed in the present study, of which 4452 had no a priori known familial mutation. The majority of participants (68.6%) were genotyped because of personal history of cancer; 20.6% were tested because of family history of cancer, and details for the remaining 10.7% were missing. Overall, 256/4452 (5.8%) carriers were detected, 141 BRCA1 and 115 BRCA2 mutation carriers. In 54% of cancer-free carriers, no clinically suspicious family history of cancer was ascertained. CONCLUSIONS: The currently used scheme of first-pass genotyping in Israel seems to have a high yield of mutation detection even in the absence of a significant family history of cancer. The challenge is to optimize the currently used targeted panel of common mutations and adjust it to the accumulating new data in the Israeli population.
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: Rita K Schmutzler; Eitan Friedman; Eric Hahnen; Corinna Ernst; Julika Borde; Yael Laitman; Britta Blümcke; Dieter Niederacher; Konstantin Weber-Lassalle; Christian Sutter; Andreas Rump; Norbert Arnold; Shan Wang-Gohrke; Judit Horváth; Andrea Gehrig; Gunnar Schmidt; Véronique Dutrannoy; Juliane Ramser; Julia Hentschel; Alfons Meindl; Christopher Schroeder; Barbara Wappenschmidt; Christoph Engel; Karoline Kuchenbaecker Journal: BMC Cancer Date: 2022-06-27 Impact factor: 4.638