ABSTRACT
PURPOSE: IPMN (Intraductal papillary mucinous neoplasm) is frequently reported in combination with a variety of extrapancreatic tumors. The IPMN in these patients might represent the phenotypes of genes associated with multiple tumor syndrome. The aim of this study was to confirm the presence of germline mutations in the p53, MLH1, MSH2, BRCA1/2, and E-cadherin genes known to be associated with gastrointestinal malignancies in hereditary tumor syndromes such as Li-Fraumeni syndrome, HNPCC, Hereditary Breast/Ovarian cancer, and Hereditary diffuse gastric cancer. METHODS: 14 patients with IPMN with extrapancreatic tumors (6 gastric cancers, 5 colorectal cancers, 1 gastric GIST, 2 hepatocellular carcinomas, 1 AoV cancer) who underwent resection were enrolled in this study. We performed PCR (Polymerase chain reaction) and direct sequencing analysis for the p53, MLH1, MSH2 and CDH-1 genes. Multiplex PCR, F-CSGE (fluorescent conformation sensitive gel electrophoresis) and direct sequencing was performed for BRCA1/2 genes. RESULTS: We identified two novel mutations in the p53 gene (exon 1, codon 31, GTC>CTC, Glu-->Gln) and the CDH-1 gene (exon 14, codon 2218, CCC>TCC, Pro-->Ser). For BRCA1, we identified 11 identical coding SNP (exon 11, codon 3232, AAG>AGG, Glu-->Gly) among 13 patients with a high allele frequency (46.1%) compared with the 30.1% reported in Korean breast cancer patients. For BRCA2, we identified a coding SNP with an allele frequency of 2.6% (exon 11, codon 2578, AAG>AGG, Met-->Val). CONCLUSION: Germline alterations of the p53 and E-Cadherin genes in IPMN patients with extrapancreatic cancer suggest that IPMN could be a manifestation of multiple tumor syndrome.