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

被引:209
作者
Sato, N
Rosty, C
Jansen, M
Fukushima, N
Ueki, T
Yeo, CJ
Cameron, JL
Iacobuzio-Donahue, CA
Hruban, RH
Goggins, M
机构
[1] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA
[3] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA
[4] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA
关键词
D O I
10.1016/S0002-9440(10)63053-2
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as weft as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of som IPMNs.
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页码:2017 / 2022
页数:6
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