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Mutational landscape of splicing genes and functional consequences across 33 cancer types

ABSTRACT: Hotspot mutations in the spliceosome component genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of this pathway in cancer. However, a comprehensive survey of splicing factor mutations across tumor types has not yet been performed. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA) in order to discover recurrent mutations in spliceosome components, identifying 119 genes with significant non-silent mutation patterns, including mutation overrepresentation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). We used RNA sequencing data to identify altered splicing events associated with these spliceosome mutations. In addition, we were able to discover common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of the splicing pathway is common in solid tumors and may represent an underappreciated hallmark of tumorigenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100530 | GEO | 2017/12/20

SECONDARY ACCESSION(S): PRJNA392042

REPOSITORIES: GEO

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Distinct and convergent consequences of splice factor mutations in myelodysplastic syndromes

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