20 research outputs found
Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas
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
Mitosis futures: the past is prologue
The mechanisms by which cells organize and segregate their chromosomes have been under close scrutiny for years, and significant progress has been made in understanding how mitosis works. Modern cell biology has identified most of the molecules that underlie mitotic spindle function, but the ways in which they are organized and controlled to make an effective and accurate cellular machine are exciting subjects for future study