Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer
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摘要Whole-genome and transcriptome sequencing were used to discover novel gene fusions in a case of colon cancer. A tumor-specific LACTB2-NCOA2 fusion originating from intra-chromosomal rearrangement of chromosome 8 was identified at both DNA and RNA levels. Unlike conventional oncogenic chimeric proteins, the fusion product lacks functional domain from respective genes, indicative of an amorphic rearrangement. This chimeric LACTB2-NCOA2 transcript was detected in 6 out of 99 (6.1%) colorectal cancer (CRC) cases, where NCOA2 was significantly downregulated. Enforced expression of wild-type NCOA2 but not the LACTB2-NCOA2 fusion protein impaired the pro-tumorigenic phenotypes of CRC cells, whereas knockdown of endogenous NCOA2 in normal colonocytes had opposite effects. Mechanistically, NCOA2 inhibited Wnt/beta-catenin signaling through simultaneously upregulating inhibitors and downregulating stimulators of Wnt/beta-catenin pathway. Collectively, our data supports that NCOA2 is a novel negative growth regulatory gene repressing the Wnt/beta-catenin pathway in CRC, where recurrent fusion with LACTB2 contributes to its disruption.
著者Yu J, Wu WKK, Liang Q, Zhang N, He J, Li X, Zhang X, Xu L, Chan MTV, Ng SSM, Sung JJY
期刊名稱Oncogene
出版年份2016
月份1
日期14
卷號35
期次2
出版社Nature Publishing Group: Open Access Hybrid Model Option B
頁次187 - 195
國際標準期刊號0950-9232
電子國際標準期刊號1476-5594
語言英式英語
Web of Science 學科類別Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Oncology

上次更新時間 2020-27-11 於 01:28