Germline mutations in BRIP1 and PALB2 in Jewish high cancer risk families

Irene Catucci, Roni Milgrom, Anya Kushnir, Yael Laitman, Shani Paluch-Shimon, Sara Volorio, Filomena Ficarazzi, Loris Bernard, Paolo Radice, Eitan Friedman, Paolo Peterlongo

Research output: Contribution to journalArticlepeer-review


Germline mutations in BRCA1 and BRCA2 account for ~30 % of inherited breast cancer. BRIP1 and PALB2 are likely genes for breast cancer susceptibility, based on their roles in maintaining cellular integrity. Indeed, few pathogenic germline mutations in both genes are reported in ethnically diverse breast cancer families. There is a paucity of data on the putative contribution of both genes to inherited breast cancer in Jewish high risk families. High risk Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were screened for BRIP1 germline mutations by combined denaturing gradient gel electrophoresis, high resolution melting and sequencing. Direct sequencing of exons and flanking intronic sequences was used for PALB2 mutational analysis. Overall, 149 women, all of high risk, cancer prone families of Ashkenazi origin, were genotyped for BRIP1 mutations: 127 with breast cancer, 22 with ovarian cancer. No truncating mutations were noted and one novel (p.Ala745Thr) and two previously described missense mutations were detected. For PALB2, 93 women were genotyped (87 with breast cancer) of Ashkenazi (n = 32) and non Ashkenazi Jewish origin. Fifteen sequence variants were detected, of these, none was truncating, four were not previously reported, and two (p.Asp871Gly and p.Leu1119Pro) were seemingly pathogenic based on the PolyPhen2 protein prediction algorithm. These missense mutations were not detected in any of 113 healthy Ashkenazi and 109 Moroccan, cancer free controls. In conclusion, germline mutations in BRIP1 and PALB2 contribute marginally to breast cancer susceptibility in ethnically diverse, Jewish high risk families.

Original languageEnglish
Pages (from-to)483-491
Number of pages9
JournalFamilial Cancer
Issue number3
Publication statusPublished - Sep 2012


  • Breast cancer risk
  • BRIP1
  • Germline mutations
  • Jewish population
  • PALB2

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)


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