Frequent miRNA-convergent fusion gene events in breast cancer

• DOI: 10.1038/s41467-017-01176-1
• Publication Date: 2017-09-29T19:40:24Z
• Authors: Helena Persson; Rolf Søkilde; Jari Häkkinen; Anna Chiara Pirona; Johan Vallon-Chri...; Anders Kvist; Fredrik Mertens; Åke Borg; Felix Mitelman; Mattias Höglund; Carlos Rovira
• Keywords: 0301 basic medicine; Science; Q; Breast Neoplasms; Article; Introns; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Humans; Female; RNA, Messenger; Gene Fusion; Promoter Regions, Genetic

AbstractStudies of fusion genes have mainly focused on the formation of fusions that result in the production of hybrid proteins or, alternatively, on promoter-switching events that put a gene under the control of aberrant signals. However, gene fusions may also disrupt the transcriptional control of genes that are encoded in introns downstream of the breakpoint. By ignoring structural constraints of the transcribed fusions, we highlight the importance of a largely unexplored function of fusion genes. Here, we show, using breast cancer as an example, that miRNA host genes are specifically enriched in fusion genes and that many different, low-frequency, 5ʹ partners may deregulate the same miRNA irrespective of the coding potential of the fusion transcript. These results indicate that the concept of recurrence, defined by the rate of functionally important aberrations, needs to be revised to encompass convergent fusions that affect a miRNA independently of transcript structure and protein-coding potential.