Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

作者：Toru Furukawa, Yuko Kuboki, Etsuko Tanji, Shoko Yoshida, Takashi Hatori, Masakazu Yamamoto, Noriyuki Shibata, Kyoko Shimizu, Naoyuki Kamatani, Keiko Shiratori · 发表于：Scientific Reports · 年份：2011 · DOI：10.1038/srep00161 · 被引用次数：441 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Genomics and Diagnostics、Neuroendocrine Tumor Research Advances

Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN.