近日,，新加坡和泰國的科學家在本周出版的《自然—遺傳學》（Nature Genetics ）上撰文稱，他們對一種與肝吸蟲有關(guān)的致命膽管癌進行了全基因組外顯子測序,。膽管癌在全球的原發(fā)性肝癌中占10%到25%的比例，高發(fā)于東南亞地區(qū),，其與麝貓后睪吸蟲感染有關(guān),。
Bin Tean Teh等人從由麝貓后睪吸蟲感染所致的膽管癌患者中提取8個腫瘤樣本以及對應(yīng)的正常組織樣本，然后進行全基因組外顯子測序分析,。
他們對46個附加病例中的15個基因進行篩查,，以檢查突變發(fā)生率。研究人員鑒定出幾種相關(guān)已知基因產(chǎn)生的體細胞突變,，同時,，還有與膽管癌突變有關(guān)的10種新基因。這意味著膽管癌發(fā)展過程中的突變可能會對基因組穩(wěn)定性,、G蛋白信號通路和組織蛋白修飾三方面產(chǎn)生影響,。（生物谷Bioon.com）
doi:10.1038/ng.2273
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Exome sequencing of liver fluke–associated cholangiocarcinoma
Choon Kiat Ong,1, 2, 14 Chutima Subimerb,1, 2, 3, 14 Chawalit Pairojkul,3 Sopit Wongkham,3 Ioana Cutcutache,4 Willie Yu,1, 2, 5 John R McPherson,4 George E Allen,1, 2 Cedric Chuan Young Ng,1, 2 Bernice Huimin Wong,1, 2 Swe Swe Myint,1, 2 Vikneswari Rajasegaran,1, 2 Hong Lee Heng,1, 2 Anna Gan,1, 2 Zhi Jiang Zang,2, 6 Yingting Wu,4, 7 Jeanie Wu,2 Ming Hui Lee,2 DaChuan Huang,1, 2 Pauline Ong,1, 2 Waraporn Chan-on,1, 2, 3 Yun Cao,8 Chao-Nan Qian,8 Kiat Hon Lim,9 Aikseng Ooi,10
Opisthorchis viverrini–related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini–related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8–3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini–related CCA.
