Breast Cancer Research and Treatment

, Volume 167, Issue 3, pp 697–702 | Cite as

The yield of targeted genotyping for the recurring mutations in BRCA1/2 in Israel

  • Rinat Bernstein-Molho
  • Yael Laitman
  • Hagit Schayek
  • Orit Reish
  • Shira Lotan
  • Sara Haim
  • Jamal Zidan
  • Eitan Friedman
Clinical Trial

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.

Keywords

BRCA1 BRCA2 germline mutations First-pass genotyping Unselected screening Hereditary breast cancer 

Notes

Conflict of interest

All authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Rinat Bernstein-Molho
    • 1
    • 4
  • Yael Laitman
    • 2
  • Hagit Schayek
    • 2
  • Orit Reish
    • 3
    • 4
  • Shira Lotan
    • 3
  • Sara Haim
    • 3
  • Jamal Zidan
    • 5
    • 6
  • Eitan Friedman
    • 2
    • 4
  1. 1.Breast Cancer Center, Oncology InstituteChaim Sheba Medical CenterRamat GanIsrael
  2. 2.Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human GeneticsChaim Sheba Medical CenterRamat GanIsrael
  3. 3.Genetic InstituteAssaf Harofeh Medical CenterZerifinIsrael
  4. 4.Sackler School of MedicineTel-Aviv UniversityTel AvivIsrael
  5. 5.The Oncology DivisionZiv Medical CenterSafedIsrael
  6. 6.Faculty of Medicine in the GalileeBar-Ilan UniversitySafedIsrael

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