Mutation analysis of the PALB2 gene in unselected pancreatic cancer patients in the Czech Republic
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
27106063
DOI
10.1016/j.cancergen.2016.03.003
PII: S2210-7762(16)30038-2
Knihovny.cz E-resources
- Keywords
- PALB2 gene, Pancreatic ductal adenocarcinoma, hereditary mutations,
- MeSH
- Carcinoma, Pancreatic Ductal genetics MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Nuclear Proteins genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation * MeSH
- DNA Mutational Analysis MeSH
- Tumor Suppressor Proteins genetics MeSH
- Pancreatic Neoplasms epidemiology genetics MeSH
- Fanconi Anemia Complementation Group N Protein MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- Nuclear Proteins MeSH
- Tumor Suppressor Proteins MeSH
- PALB2 protein, human MeSH Browser
- Fanconi Anemia Complementation Group N Protein MeSH
Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among common solid cancer diagnoses. It has been shown that up to 10% of PDAC cases have a familial component. Characterization of PDAC-susceptibility genes could reveal high-risk individuals and patients that may benefit from tailored therapy. Hereditary mutations in PALB2 (Partner and Localizer of BRCA2) gene has been shown to predispose, namely to PDAC and breast cancers; however, frequencies of mutations vary among distinct geographical populations. Using the combination of sequencing, high-resolution melting and multiplex ligation-dependent probe amplification analyses, we screened the entire PALB2 gene in 152 unselected Czech PDAC patients. Truncating mutations were identified in three (2.0%) patients. Genotyping of found PALB2 variants in 1226 control samples revealed one carrier of PALB2 truncating variant (0.08%; P = 0.005). The mean age at PDAC diagnosis was significantly lower among PALB2 mutation carriers (51 years) than in non-carriers (63 years; P = 0.016). Only one patient carrying germline PALB2 mutation had a positive family breast cancer history. Our results indicate that hereditary PALB2 mutation represents clinically considerable genetic factor increasing PDAC susceptibility in our population and that analysis of PALB2 should be considered not only in PDAC patients with familial history of breast or pancreatic cancers but also in younger PDAC patients without family cancer history.
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