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PALB2 mutations in familial breast and pancreatic cancer

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Section of Medical Oncology, Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, PO Box 208032, New Haven, CT, 06520-8032, USA

    Erin W. Hofstatter

  2. Division of Medical Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Susan M. Domchek, Leigh Boghossian & Katherine L. Nathanson

  3. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Alexander Miron & Penelope L. Miron

  4. Division of Population Sciences and Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Judy Garber

  5. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Molin Wang

  6. Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Kathryn Componeschi & Nadine Tung

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  1. Erin W. Hofstatter
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  2. Susan M. Domchek
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  3. Alexander Miron
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  4. Judy Garber
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  5. Molin Wang
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  6. Kathryn Componeschi
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  7. Leigh Boghossian
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  8. Penelope L. Miron
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  9. Katherine L. Nathanson
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  10. Nadine Tung
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Correspondence to Erin W. Hofstatter.

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Hofstatter, E.W., Domchek, S.M., Miron, A. et al. PALB2 mutations in familial breast and pancreatic cancer. Familial Cancer 10, 225–231 (2011). https://doi.org/10.1007/s10689-011-9426-1

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  • DOI: https://doi.org/10.1007/s10689-011-9426-1

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