下一代测序揭示TP53突变是导管内乳头状黏液性肿瘤的恶性标志物，可通过胰液检测到。

Next-Generation Sequencing Revealed TP53 Mutations to Be Malignant Marker for Intraductal Papillary Mucinous Neoplasms That Could Be Detected Using Pancreatic Juice.

作者信息

Takano Shinichi, Fukasawa Mitsuharu, Kadokura Makoto, Shindo Hiroko, Takahashi Ei, Hirose Sumio, Maekawa Shinya, Mochizuki Kunio, Kawaida Hiromichi, Itakura Jun, Katoh Ryohei, Fujii Hideki, Sato Tadashi, Enomoto Nobuyuki

机构信息

From the *First Department of Internal Medicine, †Department of Pathology, and ‡First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Japan.

出版信息

Pancreas. 2017 Nov/Dec;46(10):1281-1287. doi: 10.1097/MPA.0000000000000931.

DOI:10.1097/MPA.0000000000000931

PMID:28930868

Abstract

OBJECTIVES

The aims of this study were to identify the genetic mutations associated with malignant intraductal papillary mucinous neoplasms (IPMNs) and evaluate the possibility of detecting mutations in pure pancreatic juice by next-generation sequencing.

METHODS

Resected tissues were collected from 50 patients with IPMN, and pure pancreatic juice samples were collected from 19 patients who had a resection. The extracted DNA was amplified by multiplex polymerase chain reaction targeting 52 cancer-related genes, including KRAS, GNAS, RNF43, and TP53; the mutations were then detected by next-generation sequencing and then analyzed for correlations with the clinicopathological characteristics.

RESULTS

In the resected tissues, the most frequently detected mutations were in KRAS, GNAS, TP53, and RNF43, in 88%, 76%, 36%, and 30% of cases, respectively. Univariate and multivariate analyses revealed that only TP53 mutations were associated with malignant IPMNs (P = 0.023). In the pure pancreatic juice, TP53 mutations were detected in 5 of 10 resected samples with malignant IPMN and in 4 of 5 pancreatic juice samples with mutation in resected samples.

CONCLUSIONS

From 52 cancer-related gene analysis, only TP53 mutation was associated with malignant IPMNs. TP53 mutation could also be detected in pure pancreatic juice, potentially making it a useful tool to diagnose malignant IPMNs preoperatively.

摘要

目的

本研究旨在鉴定与恶性导管内乳头状黏液性肿瘤（IPMN）相关的基因突变，并评估通过下一代测序在纯胰液中检测突变的可能性。

方法

收集50例IPMN患者的切除组织，并从19例接受切除术的患者中收集纯胰液样本。提取的DNA通过针对52个癌症相关基因（包括KRAS、GNAS、RNF43和TP53）的多重聚合酶链反应进行扩增；然后通过下一代测序检测突变，并分析其与临床病理特征的相关性。

结果

在切除组织中，最常检测到的突变分别在KRAS、GNAS、TP53和RNF43基因中，发生率分别为88%、76%、36%和30%。单因素和多因素分析显示，只有TP53突变与恶性IPMN相关（P = 0.023）。在纯胰液中，10例切除的恶性IPMN样本中有5例检测到TP53突变，5例切除样本中有突变的胰液样本中有4例检测到TP53突变。