Aberrant somatic hypermutation of CCND1 generates non-coding drivers of mantle cell lymphomagenesis.

ABSTRACT: Aberrant somatic hypermutation (aSHM) can target proto-oncogenes and drive oncogenesis. In mantle cell lymphoma (MCL), CCND1 is targeted by aSHM in the non-nodal subtype (nnMCL), giving rise to exon1 encoded mutant proteins like E36K, Y44D, and C47S that contribute to lymphomagenesis by virtue of their increased protein stability and nuclear localization. However, the vast majority of somatic variants generated by aSHM are found in the first intron of CCND1 but their significance for mantle cell lymphomagenesis is unknown. We performed whole-genome and whole-transcriptome sequencing in 84 MCL patients to explore the contribution of non-coding somatic variants created by aSHM to lymphomagenesis. We show that non-coding variants are enriched in a MCL specific manner in transcription factor-b

SUBMITTER: Muller H 

PROVIDER: S-EPMC9113931 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature