Are PALB2 mutations associated with increased risk of male breast cancer?

BRCA2 and PALB2 function together in the Fanconi anemia (FA)-Breast Cancer (BRCA) pathway. Mono-allelic and bi-allelic BRCA2 and PALB2 mutation carriers share many clinical characteristics. Mono-allelic germline mutations of BRCA2 and PALB2 are risk alleles of female breast cancer and have also been reported in familial pancreatic cancer, and bi-allelic mutations cause a severe form of Fanconi anemia. In view of these similarities, we investigated whether the prevalence of PALB2 mutations was increased in breast cancer families with the occurrence of BRCA2 associated tumours other than female breast cancer. PALB2 mutation analysis was performed in 110 non-BRCA1/2 cancer patients: (a) 53 ovarian cancer patients from female breast-and/or ovarian cancer families; (b) 45 breast cancer patients with a first or second degree relative with pancreatic cancer; and (c) 12 male breast cancer patients from female breast cancer families. One truncating PALB2 mutation, c.509_510delGA, resulting in p.Arg170X, was found in a male breast cancer patient. We conclude that germline mutations of PALB2 do not significantly contribute to cancer risk in non-BRCA1/2 cancer families with at least one patient with ovarian cancer, male breast cancer, and/or pancreatic cancer.

Section: Discussionmentioning

confidence: 69%

PALB2 analysis in BRCA2-like families

Adank

Mil

Gille

et al. 2010

“…An interesting evaluation about this latter is provided in the recent article by Sauty de Chalon et al [8]. Yet in the above mentioned study PALB2 pathogenic mutations were not found in 25 MBCs belonging to 25 BRCA1/2 negative families and, based on PALB2 mutation frequency (*1%), it cannot be excluded that these findings may indeed be due to the small series analysed.…”

mentioning

confidence: 87%

PALB2 mutations in male breast cancer: a population-based study in Central Italy

Silvestri

Rizzolo

Zanna

et al. 2010

“…Its biallelic inactivation results in Fanconi anemia, while the presence of a germline mutation in the heterozygous state is associated with increased risk of breast, pancreatic, and possibly some other cancers (Table 1 and references therein). The geographical spread of PALB2 mutations has not been comprehensively analyzed yet, and several recent studies have failed to identify any PALB2 mutations in breast cancer series from their population [24–27]. The search for breast cancer predisposing mutations is considered to be particularly effective in patient series with a pronounced family history of the disease.…”

Section: Introductionmentioning

confidence: 99%

PALB2 mutations in German and Russian patients with bilateral breast cancer

Bogdanova

Sokolenko

Iyevleva

et al. 2010

Since germline mutations in the PALB2 (Partner and Localizer of BRCA2) gene have been identified as breast cancer (BC) susceptibility alleles, the geographical spread and risks associated with PALB2 mutations are subject of intense investigation. Patients with bilateral breast cancer constitute a valuable group for genetic studies. We have thus scanned the whole coding region of PALB2 in a total of 203 German or Russian bilateral breast cancer patients using an approach based on high-resolution melting analysis and direct sequencing of genomic DNA samples. Truncating PALB2 mutations were identified in 4/203 (2%) breast cancer patients with bilateral disease. The two nonsense mutations, p.E545X and p.Q921X, have not been previously described whereas the two other mutations, p.R414X and c.509_510delGA, are recurrent. Our results indicate that PALB2 germline mutations account for a small, but not negligible, proportion of bilateral breast carcinomas in German and Russian populations.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-010-1290-4) contains supplementary material, which is available to authorized users.