Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer
Publication in refereed journal


香港中文大学研究人员 ( 现职)

于君教授 (内科及药物治疗学系)

沈祖尧教授 (内科及药物治疗学系)

吴兆文教授 (外科学系)

陈德威教授 (麻醉及深切治疗学系)

张翔博士 (内科及药物治疗学系)

张宁先生 (内科及药物治疗学系)

梁巧仪教授 (内科及药物治疗学系)

胡嘉麒教授 (麻醉及深切治疗学系)

全文

数位物件识别号 (DOI) ○○@http://aims.cuhk.edu.hk/converis/portal/Publication/1http://aims.cuhk.edu.hk/converis/portal/Publication/1$@○○

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Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/1WOS source URL

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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.http://aims.cuhk.edu.hk/converis/portal/Publication/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.

着者Yu J, Wu WKK, Liang Q, Zhang N, He J, Li X, Zhang X, Xu L, Chan MTV, Ng SSM, Sung JJY
期刊名称Oncogene
出版年份20http://aims.cuhk.edu.hk/converis/portal/Publication/16
月份http://aims.cuhk.edu.hk/converis/portal/Publication/1
日期http://aims.cuhk.edu.hk/converis/portal/Publication/14
卷号35
期次2
出版社Nature Publishing Group: Open Access Hybrid Model Option B
页次http://aims.cuhk.edu.hk/converis/portal/Publication/187 - http://aims.cuhk.edu.hk/converis/portal/Publication/195
国际标準期刊号0950-9232
电子国际标準期刊号http://aims.cuhk.edu.hk/converis/portal/Publication/1476-5594
语言英式英语

Web of Science 学科类别Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Oncology