研究背景
胃癌是全世界發(fā)病率第五、腫瘤死亡率高居第三的常見惡性腫瘤[1]。其中，大約有40%胃癌發(fā)生于中國，多數(shù)人被診斷為胃癌時已是進(jìn)展期，更容易轉(zhuǎn)移或者復(fù)發(fā)[2]。無論是早期胃癌還是晚期胃癌，腹膜轉(zhuǎn)移都是最常見的轉(zhuǎn)移或者復(fù)發(fā)方式[3-5]。由于目前沒有有效的治療手段，胃癌一旦發(fā)生腹膜轉(zhuǎn)移，患者的中位生存時間不足6個月，因此，闡明胃癌腹膜轉(zhuǎn)移的分子機(jī)制改善其預(yù)后是亟待解決的問題。
二代測序作為精準(zhǔn)醫(yī)療的關(guān)鍵技術(shù)，可發(fā)現(xiàn)腫瘤相關(guān)的靶基因，為個體化治療提供靶標(biāo)，使得腫瘤的研究發(fā)生重要變革[6, 7]。全外顯子測序(WES)針對人類基因組的1%進(jìn)行測序，可獲得較好的測序深度，有利于發(fā)現(xiàn)轉(zhuǎn)移灶基因改變的信息[8-10]。
胃腺癌是胃癌最常見的組織類型，一旦發(fā)生腹膜轉(zhuǎn)移，手術(shù)將不再作為最優(yōu)的治療手段，因此，同時獲取胃癌原發(fā)灶和配對的轉(zhuǎn)移灶變得極為困難。然而，近年來，減瘤手術(shù)被認(rèn)為是一種可以是腹膜轉(zhuǎn)移生存患者獲益的治療方式[9]。本研究選取一例胃腺癌患者的原發(fā)灶，腹膜轉(zhuǎn)移灶以及各自配對的正常組織，進(jìn)行全外顯子測序，旨在發(fā)現(xiàn)胃癌腹膜轉(zhuǎn)移的突變基因。


研究思路

研究結(jié)果
我們選用llumminaHiSeq2500測序儀，雙端測序，讀長100nt，用WES測序發(fā)現(xiàn)了胃癌原發(fā)灶的48個體細(xì)胞單核苷酸突變（SNP），腹膜轉(zhuǎn)移灶49個SNP,G>A和C>T是突變頻率最高的類型（圖1）。通過Sanger測序分別驗證了原發(fā)灶和轉(zhuǎn)移灶中的SNP，原發(fā)灶和腹膜轉(zhuǎn)移灶中的非同義體細(xì)胞突變分別有27和35個得到驗證（圖2，3）。并同體細(xì)胞突變數(shù)據(jù)庫COSMIC中的胃癌數(shù)據(jù)經(jīng)行了比較，發(fā)現(xiàn)了突變頻率高于5%的基因（BAI1,ARID2,THSD1,KIAA2022），以及尚未在該數(shù)據(jù)庫中出現(xiàn)的突變基因，還有部分SNP僅僅發(fā)生腹膜轉(zhuǎn)移灶（ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16, NCAMI），他們可能是胃癌發(fā)生腹膜轉(zhuǎn)移的驅(qū)動基因，其機(jī)制有待進(jìn)一步研究。因此，我們發(fā)現(xiàn)胃癌腹膜轉(zhuǎn)移灶中的大多數(shù)非同義體細(xì)胞突都與原發(fā)灶相同，有少數(shù)是不同于原發(fā)灶突變。該研究中全外顯子測序服務(wù)及數(shù)據(jù)分析服務(wù)由上海伯豪生物技術(shù)有限公司提供。

參考文獻(xiàn)
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原文出處
Liu H, Li F, Zhu Y, Li T, Huang H, Lin T, Hu Y, Qi X, Yu J, Li G. Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study. Oncotarget.2016.