Lack of germline PALB2 mutations in melanoma-prone families with CDKN2A mutations and pancreatic cancer
- 147 Downloads
The presence of pancreatic cancer (PC) in melanoma-prone families has been consistently associated with an increased frequency of CDKN2A mutations, the major high-risk susceptibility gene identified for melanoma. However, the precise relationship between CDKN2A, melanoma and PC remains unknown. We evaluated a recently identified PC susceptibility gene PALB2 using both sequencing and tagging to determine whether PALB2 might explain part of the relationship between CDKN2A, melanoma, and PC. No disease-related mutations were identified from sequencing PALB2 in multiple pancreatic cancer patients or other mutation carrier relatives of PC patients from the eight melanoma-prone families with CDKN2A mutations and PC. In addition, no significant associations were observed between 11 PALB2 tagging SNPs and melanoma risk in 23 melanoma-prone families with CDKN2A mutations or the subset of 11 families with PC or PC-related CDKN2A mutations. The results suggested that PALB2 does not explain the relationship between CDKN2A, melanoma, and pancreatic cancer in these melanoma-prone families.
KeywordsCDKN2A PALB2 Familial melanoma Pancreatic cancer Germline mutation
We are indebted to the participating families, whose generosity and cooperation have made this study possible. We also acknowledge the contributions to this work that were made by Virginia Pichler, Deborah Zametkin, and Mary Fraser. This research was supported by the Intramural Research Program of the NIH, NCI, DCEG.
Conflict of interest
The authors declare no conflict of interest.
- 6.The Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91(15):1310–1316Google Scholar
- 13.Sabbaghian N, Kyle R, Hao A, Hogg D, Tischkowitz M (2010) Mutation analysis of the PALB2 cancer predisposition gene in familial melanoma. Fam Cancer. doi: 10.1007/s10689-010-9405-y
- 14.Hofstatter EW, Domchek SM, Miron A, Garber J, Wang M, Componeschi K, Boghossian L, Miron PL, Nathanson KL, Tung N (2011) PALB2 mutations in familial breast and pancreatic cancer. Fam Cancer. doi: 10.1007/s10689-011-9426-1
- 15.Stadler ZK, Salo-Mullen E, Sabbaghian N, Simon JA, Zhang L, Olson SH, Kurtz R, Offit K, Foulkes WD, Robson ME, Tischkowitz M (2011) Germline PALB2 mutation analysis in breast-pancreas cancer families. J Med Genet. doi: 10.1136/jmg.2010.087379