Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo C J, Cameron J L, Iacobuzio-Donahue C A, Hruban R H, Goggins M
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Am J Pathol. 2001 Dec;159(6):2017-22. doi: 10.1016/S0002-9440(10)63053-2.
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 well 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 some IPMNs.
尽管临床医生对胰腺导管内乳头状黏液性肿瘤（IPMNs）的认识日益提高，但IPMNs的分子特征尚未得到很好的描述。先前的报告表明，STK11/LKB1（一种与黑斑息肉综合征（PJS）相关的肿瘤抑制基因）的失活在胃肠道错构瘤以及包括胰腺腺癌在内的几种癌症的发病机制中起作用。我们使用聚合酶链反应扩增来自包含STK11/LKB1基因的19p13.3区域的五个微卫星标记，分析了22个IPMNs的DNA以检测杂合性缺失（LOH）。在患有PJS的患者的2个IPMNs中有2个（100%）检测到19p13.3处的LOH，在缺乏PJS特征的患者的20个IPMNs中有5个（25%）检测到（22个中有7个，总体为32%）。对这些具有LOH的IPMNs中的STK11/LKB1基因进行测序分析发现，在一名患有PJS的患者的一个IPMN中存在种系突变，在20个散发性IPMNs中的1个中存在体细胞突变。22个IPMNs中均未显示STK11/LKB1基因的高甲基化。这些结果表明，STK11/LKB1基因参与了一些IPMNs的发病机制。
