Familial Cancer

, Volume 10, Issue 2, pp 225–231 | Cite as

PALB2 mutations in familial breast and pancreatic cancer

  • Erin W. Hofstatter
  • Susan M. Domchek
  • Alexander Miron
  • Judy Garber
  • Molin Wang
  • Kathryn Componeschi
  • Leigh Boghossian
  • Penelope L. Miron
  • Katherine L. Nathanson
  • Nadine Tung


PALB2 (Partner And Localizer of BRCA2) binds to and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1–2% of familial breast cancer and 3–4% of familial pancreatic cancer cases. The goal of this study was to evaluate the prevalence of PALB2 mutations in women with breast cancer without BRCA1/2 mutations who also had a personal or family history of pancreatic cancer. PALB2 mutation analysis was performed in 94 non-BRCA1/2 breast cancer patients with a personal or family history of pancreatic cancer. Two truncating PALB2 mutations, c.3549C>CA and c.2962C>CT, were identified resulting in a mutation prevalence of 2.1%. The proband found to carry the c.3549C>CA PALB2 mutation had a mother diagnosed with both breast and pancreatic cancer; this relative was subsequently confirmed to carry the identical mutation. The proband with the c.2962C>CT mutation had a father and paternal aunt diagnosed with pancreatic cancer; neither relative was available for testing. Two novel PALB2 missense variants were also found, one of which was deemed potentially deleterious. The prevalence rate of PALB2 mutations in a non-BRCA1/2 breast cancer population specifically selected for a family history of pancreatic cancer does not appear to be significantly increased compared to that observed in other breast cancer populations studied thus far. Further evaluation is needed to determine the prevalence of PALB2 mutations and the clinical utility of such testing in those individuals affected with both breast and pancreatic cancers.


BRCA2 Breast cancer PALB2 Pancreatic cancer 



This work was supported by grants from the Breast Cancer Research Foundation (to KLN, NT, and JG); the Dana Farber/Harvard Cancer Center (CA 006516); the Dana Farber/Harvard Cancer Center Breast SPORE (CA 089393); and the MacDonald Family Foundation (to SMD).


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Erin W. Hofstatter
    • 1
  • Susan M. Domchek
    • 2
  • Alexander Miron
    • 3
  • Judy Garber
    • 4
  • Molin Wang
    • 5
  • Kathryn Componeschi
    • 6
  • Leigh Boghossian
    • 2
  • Penelope L. Miron
    • 3
  • Katherine L. Nathanson
    • 2
  • Nadine Tung
    • 6
  1. 1.Section of Medical OncologyYale Cancer Center, Yale School of MedicineNew HavenUSA
  2. 2.Division of Medical Oncology, Abramson Cancer CenterUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Cancer BiologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Division of Population Sciences and Adult OncologyDana-Farber Cancer InstituteBostonUSA
  5. 5.Department of Biostatistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  6. 6.Division of Hematology-OncologyBeth Israel Deaconess Medical CenterBostonUSA

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