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Ong CK Subimerb C Pairojkul C Wongkham S Cutcutache I Yu W McPherson JR Allen GE Ng CC Wong BH Myint SS Rajasegaran V Heng HL Gan A Zang ZJ Wu Y Wu J Lee MH Huang D Ong P Chan-on W Cao Y Qian CN Lim KH Ooi A Dykema K Furge K Kukongviriyapan V Sripa B Wongkham C Yongvanit P Futreal PA Bhudhisawasdi V Rozen S Tan P Teh BT 《Nature genetics》2012,44(6):690-693
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. 相似文献
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CHEN Yen-Chieh SUNG Quocheng CHEN Chao-Nan 《科学通报(英文版)》2006,51(22):2789-2794
Stream-power incision model has always been applied to detecting the steady-state situation of ranges. Oblique arc-continent collision occurring during the period of Penglai Orogeny caused the Taiwan mountain belt to develop landscape of three evolution stages, namely stages of pre-steady-state (growing ranges in southern Taiwan), steady-state (ranges in central Taiwan) and post-steady-state (decaying ranges in northern Taiwan). In the analysis on streams of the Taiwan mountain belt made by exploring the relationship between the slope of bedrock channel (S) and the catchment area (A), the topographic features of the ranges at these three stages are acquired. The S-A plot of the steady-state ranges is in a linear form, revealing that the riverbed height of bedrock channel does not change over time (dz/dt = 0). The slope and intercept of the straight line S-A are related to evolution time of steady-state topography and tectonic uplift rate respectively. The S-A plots of the southern and northern ranges of Taiwan mountain belt appear to be in convex and concave forms respectively, implying that the riverbed height of bedrock channel at the two ranges rises (dz/dt > 0) and falls (dz/dt < 0) over time respectively. Their tangent intercept can still reflect the tectonic uplift rate. This study develops an empirical stream-power erosion model of pre-steady-state and post-steady-state topography. 相似文献
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