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Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer.


ABSTRACT: 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/?-catenin signaling through simultaneously upregulating inhibitors and downregulating stimulators of Wnt/?-catenin pathway. Collectively, our data supports that NCOA2 is a novel negative growth regulatory gene repressing the Wnt/?-catenin pathway in CRC, where recurrent fusion with LACTB2 contributes to its disruption.

SUBMITTER: Yu J 

PROVIDER: S-EPMC4717154 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer.

Yu J J   Wu W K K WK   Liang Q Q   Zhang N N   He J J   Li X X   Zhang X X   Xu L L   Chan M T V MT   Ng S S M SS   Sung J J Y JJ  

Oncogene 20150330 2


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 cance  ...[more]

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