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胰腺导管内乳头状黏液性肿瘤(IPMN)病例中的突变:一种潜在的预后因素。

Mutations in IPMN Cases: A Potential Prognostic Factor.

作者信息

Chang Xiao Yan, Wu Yan, Jiang Ying, Wang Peng Yan, Chen Jie

机构信息

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100730, China.

出版信息

Gastroenterol Res Pract. 2020 Aug 31;2020:1457452. doi: 10.1155/2020/1457452. eCollection 2020.

Abstract

An intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precursor lesion, and it often harbors mutations in , , and . To clarify the molecular profiles of IPMNs, we conducted mutation analysis of , , and in 61 IPMN formalin-fixed, paraffin-embedded (FFPE) specimens. The mutation rates of codons 12, 13, and 61 in and codon 201 in were detected by Sanger sequencing. Next-generation sequencing was performed on , and the results were further verified by Sanger sequencing. We identified and mutations in 35 (57%) and 40 (66%) IPMN cases, respectively. mutations were significantly correlated with the morphologic subtype ( < 0.001) and were more prevalent in the intestinal subtype (93%) than in the gastric (55%) and pancreatobiliary subtypes (44%) but were absent in the oncocytic subtype. mutations were found in 5 cases (8%), all of which occurred in high-grade dysplasia and invasive lesions (2/5 and 3/5). All 5 cases harboring RNF43 mutations also exhibited GNAS mutations. RNF43 mutations were associated with a worse prognosis in invasive IPMN patients ( = 0.002), while KRAS and GNAS mutations did not affect the prognosis of patients.

摘要

导管内乳头状黏液性肿瘤(IPMN)是一种常见的胰腺前驱病变,且常伴有 、 和 的突变。为阐明IPMN的分子特征,我们对61例IPMN福尔马林固定、石蜡包埋(FFPE)标本进行了 、 和 的突变分析。通过桑格测序检测 中密码子12、13和61以及 中密码子201的突变率。对 进行了二代测序,并通过桑格测序进一步验证结果。我们分别在35例(57%)和40例(66%)IPMN病例中鉴定出 突变和 突变。 突变与形态学亚型显著相关(<0.001),在肠型亚型(93%)中比胃型(55%)和胰胆管型亚型(44%)更常见,但在嗜酸性细胞型亚型中不存在。在5例(8%)病例中发现了 突变,所有这些突变均发生在高级别异型增生和浸润性病变中(2/5和3/5)。所有5例携带RNF43突变的病例也表现出GNAS突变。RNF43突变与浸润性IPMN患者的预后较差相关(=0.002),而KRAS和GNAS突变不影响患者的预后。

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