Familial Cancer

, Volume 11, Issue 3, pp 483–491 | Cite as

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 FriedmanEmail author
  • Paolo Peterlongo
Original Article


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.


Germline mutations BRIP1, PALB2 Breast cancer risk Jewish population 



We thank all individuals who participated to this study. This study was partially funded by Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’). This study was partuially funded by the Israel Cancer Association. This work was done in partial fulfillment of the requirements for a Masters degree for Roni Milgrom and Anya Kushnir at the Department of Human Genetics and Molecular Biology at the Tel-Aviv University, Tel-Aviv, Israel.

Conflict of interest

All authors declare that they have no conflict of interest regarding the data published herein.

Supplementary material

10689_2012_9540_MOESM1_ESM.doc (49 kb)
Supplementary material 1 (DOC 49 kb)


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Irene Catucci
    • 1
    • 2
  • Roni Milgrom
    • 3
  • Anya Kushnir
    • 3
  • Yael Laitman
    • 3
  • Shani Paluch-Shimon
    • 4
  • Sara Volorio
    • 1
  • Filomena Ficarazzi
    • 1
  • Loris Bernard
    • 5
  • Paolo Radice
    • 1
    • 2
  • Eitan Friedman
    • 3
    • 6
    Email author
  • Paolo Peterlongo
    • 1
    • 2
  1. 1.IFOM, Fondazione Istituto FIRC di Oncologia MolecolareMilanItaly
  2. 2.Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive MedicineFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  3. 3.The Susanne Levy Gertner Oncogenetics UnitThe Danek Gertner Institute of Genetics, Chaim Sheba Medical Center, Tel-Aviv UniversityTel-HashomerIsrael
  4. 4.Institute of Human Genetics, the Oncology Institute, Tel-Aviv UniversityTel-AvivIsrael
  5. 5.Department of Experimental OncologyIstituto Europeo di OncologiaMilanItaly
  6. 6.The Sackler School of MedicineTel-Aviv UniversityTel-AvivIsrael

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