| Literature DB >> 26146084 |
Fei Yao1, Jaya P Kausalya2, Yee Yen Sia1, Audrey S M Teo1, Wah Heng Lee3, Alicia G M Ong2, Zhenshui Zhang4, Joanna H J Tan5, Guoliang Li6, Denis Bertrand3, Xingliang Liu5, Huay Mei Poh5, Peiyong Guan7, Feng Zhu8, Thushangi Nadeera Pathiraja1, Pramila N Ariyaratne3, Jaideepraj Rao9, Xing Yi Woo10, Shaojiang Cai3, Fabianus H Mulawadi3, Wan Ting Poh10, Lavanya Veeravalli11, Chee Seng Chan11, Seong Soo Lim4, See Ting Leong12, Say Chuan Neo12, Poh Sum D Choi12, Elaine G Y Chew5, Niranjan Nagarajan3, Pierre-Étienne Jacques13, Jimmy B Y So14, Xiaoan Ruan15, Khay Guan Yeoh16, Patrick Tan17, Wing-Kin Sung7, Walter Hunziker18, Yijun Ruan19, Axel M Hillmer20.
Abstract
Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed.Entities:
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Year: 2015 PMID： 26146084 DOI： 10.1016/j.celrep.2015.06.020
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423