| Literature DB >> 25407104 |
Swee Seong Wong1, Kyoung-Mee Kim2, Jason C Ting1, Kun Yu1, Jake Fu3, Shawn Liu4, Razvan Cristescu5, Michael Nebozhyn5, Lara Gong4, Yong Gang Yue1, Jian Wang1, Chen Ronghua5, Andrey Loboda5, James Hardwick5, Xiaoqiao Liu5, Hongyue Dai5, Jason Gang Jin3, Xiang S Ye1, So Young Kang2, In Gu Do2, Joon Oh Park6, Tae Sung Sohn7, Christoph Reinhard1, Jeeyun Lee6, Sung Kim7, Amit Aggarwal1.
Abstract
Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.Entities:
Mesh：
Year: 2014 PMID： 25407104 DOI： 10.1038/ncomms6477
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919