Transcriptomics

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The effects of U1 snRNA mutation in chronic lymphocytic leukemia cell lines


ABSTRACT: Despite an intensive search for non-coding cancer drivers, only a few have been discovered to date and none have been found among the RNAs contributing to the spliceosome. Here we report a highly recurrent A>C somatic mutation at the third base of U1 spliceosomal RNA in several tumour types. This mutation changes the preferential A-U base-pairing between U1 and 5′ splice site to C-G base-pairing, thereby creating novel splice junctions and altering the splice pattern of multiple genes, including those related to cancer. Clinically, the A>C mutation is associated with alcohol consumption in hepatocellular carcinoma and the aggressive IGHV unmutated subtype of chronic lymphocytic leukaemia (CLL). The U1 hotspot mutation confers an adverse prognosis to CLL patients independently, and may represent a new target for treatment. Our study demonstrates one of the first non-coding drivers in spliceosomal RNAs and reveals a novel mechanism of aberrant splicing in human cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE134197 | GEO | 2019/07/13

REPOSITORIES: GEO

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