Mutation analysis of the PALB2 gene in unselected pancreatic cancer patients in the Czech Republic.
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.
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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Borecka
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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Zemankova
Department of Oncology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
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Vocka
Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.
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Soucek
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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Soukupova
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
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Kleiblova
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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Sevcik
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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Kleibl
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. Electronic address: mjana@lf1.cuni.cz.
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Janatova
D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D004252:DNA Mutational Analysis; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
PALB2 gene; Pancreatic ductal adenocarcinoma; hereditary mutations