STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas

Despite the growing awareness of intraductal papillary-mucinous neoplasms ( IPMNs) of the pancreas among clinicians, the molecular features of IPMNs ha ve not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers sy ndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartom as as weft as several cancers, including pancreatic adenocarcinoma. Using p olymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 I PMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 o f 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lac king features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK 11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IP MN that arose in a patient with PJS and a somatic mutation in 1 of the 20 s poradic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LK B1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of som IPMNs.