Abstract
Partner and localizer of BRCA2 (PALB2), plays an important functional role in DNA damage repair. Recent studies indicate that germline mutations in PALB2 predispose individuals to a high risk of developing familial breast cancer. Therefore, comprehensive identification of PALB2 germline mutations is potentially important for understanding their roles in tumorigenesis and for testing their potential utility as clinical targets. Most of the previous studies of PALB2 have focused on familial breast cancer cases with normal/wild-type BRCA1 and BRCA2 (BRCAx). We hypothesize that PALB2 genetic mutations also exist in individuals with BRCA mutations (BRCA+). To test this hypothesis, PALB2 germline mutations were screened in 107 exome data sets collected from familial breast cancer families who were either BRCA1+ or BRCAx. Two novel heterozygous mutations predicted to alter the function of PALB2 were identified (c.2014G>C, p.E672Q and c.2993G>A, p.G998E). Notably, both of these mutations co-existed in BRCA1+ and BRCA1x families. These studies show that mutations in PALB2 can occur independent of the status of BRCA1 mutations, and they highlight the importance to include BRCA1+ families in PALB2 mutation screens.
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Abbreviations
- PALB2:
-
The partner and localizer of BRCA2
- BRCA1:
-
Breast cancer 1, early onset
- BRCA2:
-
Breast cancer 2, early onset
- MAF:
-
Minor allele frequency
- LOVD:
-
Leiden open variation database
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Acknowledgments
The authors acknowledge the Breast Cancer Collaborative Registry (BCCR), developed and maintained by the University of Nebraska Medical Center (UNMC) Biomedical Informatics Core at the Fred & Pamela Buffett Cancer Center. The study was supported by a pilot grant from the UNMC Fred & Pamela Buffett Cancer Center, an NIH Grant 1R21CA180008 (SMW), an overseas study scholarship [sponsored by China Scholarship Council (FX)], the Charles F. and Mary C. Heider Chair in Cancer Research (HL), and revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. The funding bodies play no roles in design, collection, analysis, and interpretation of data. The authors kindly thank Melody A. Montgomery at the University of Nebraska Medical Center (UNMC) Research Editorial Office for the professional editing of this manuscript.
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The authors declare that they have no competing interests.
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Bradley Downs and Yeong C. Kim have contributed equally to the study.
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Downs, B., Kim, Y.C., Xiao, F. et al. Two PALB2 germline mutations found in both BRCA1+ and BRCAx familial breast cancer. Breast Cancer Res Treat 151, 219–224 (2015). https://doi.org/10.1007/s10549-015-3358-7
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DOI: https://doi.org/10.1007/s10549-015-3358-7