STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas
STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas
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DOI：
10.1016/s0002-9440(10)63053-2
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发表时间：
2001-12-01
影响因子：
6
通讯作者：
Goggins, M
中科院分区：
文献类型：
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作者：
Sato, N;Rosty, C;Goggins, M
尽管越来越多的认识导管内乳头状粘液性肿瘤（IPMNs）的胰腺临床医生，IPMNs的分子特征还没有得到很好的表征。先前的报告表明，STK 11/LKB 1，一个负责Peutz-Jeghers综合征（PJS）的肿瘤抑制基因的失活，在胃肠道错构瘤的发病机制中起作用，如几种癌症，包括胰腺癌。利用聚合酶链反应扩增5个微卫星标记从19 p13.3区域窝藏STK 11/LKB 1基因，我们分析了DNA从22 IPMN的杂合性丢失（洛）。在22例（100%）PJS患者的IPMN和5/20例（25%）缺乏PJS特征的患者（7/22，32%）的IPMN中确定了19 p13.3的洛缺失。对这些有洛的IPMN中的STK 11/LKB 1基因进行测序分析，发现在一个PJS患者中出现的IPMN中存在种系突变，在20个散发性IPMN中的1个中存在体细胞突变。22例IPMN均未出现STK 11/LKB 1基因的高甲基化。这些结果表明STK 11/LKB 1基因参与了某些IPMNs的发病机制。
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.