PT - JOURNAL ARTICLE AU - Alejandro Reyes AU - Carolin Blume AU - Vicent Pelechano AU - Petra Jakob AU - Lars M. Steinmetz AU - Thorsten Zenz AU - Wolfgang Huber TI - Transcriptome analysis of chronic lymphoid leukemia reveals isoform regulation associated with mutations in <em>SF3B1</em> AID - 10.1101/000992 DP - 2013 Jan 01 TA - bioRxiv PG - 000992 4099 - http://biorxiv.org/content/early/2013/12/02/000992.short 4100 - http://biorxiv.org/content/early/2013/12/02/000992.full AB - Genome sequence studies of chronic lympoid leukemia (CLL) have provided a comprehensive overview of recurrent somatic mutations in coding genes. One of the most intriguing discoveries has been the prevalence of mutations in the HEAT-repeat domain of the splicing factor SF3B1. A frequently observed variant is predicted to cause the substitution of a lysine with a glutamic acid at position 700 of the protein (K700E). However, the molecular consequences of the mutations and their contribution to the cancer phenotype are largely unknown. We aimed to investigate the consequences of the K700E mutation in SF3B1 on transcript isoform regulation in CLL. We sequenced the transcriptomes of six samples: four CLL tumour cells, of which two contained the K700E mutation in SF3B1, and CD19 positive cells from two healthy donors. We identified 41 genes that showed differential usage of exons associated with the mutated status of SF3B1 (false discovery rate 10%). These genes were enriched in pathways including “interferon signaling” and “mRNA splicing”. Additionally, we found evidence of differential exon usage of the genes UQCC and RPL31 as a consequence of mutations in SF3B1 in our CLL data; notably, a similar effect on these genes was described in a previously published study of uveal melanoma. These data provide an initial view of transcript isoform consequences of the SF3B1 (K700E) mutation in CLL, some of which might contribute to the tumourigenesis of CLL. Studies of larger cohorts and model systems are required to extend these findings.