Novel Driver Synonymous Mutations in the Coding Regions of GCB Lymphoma Patients Improve the Transcription Levels of BCL2

Synonymous mutations inside the coding region which do not alter the amino acid chain are usually considered to have no effect on the protein. However, in recent years it was shown that they may regulate expression levels via various mechanisms, suggesting that they may also play an important role in tumorigenesis. In the current study, we suggest a pipeline for detecting cancerous synonymous mutations that affect the cancer fitness via regulation of transcription. We demonstrate our approach by reporting cases where cancerous synonymous mutations inside the coding regions of the gene BCL2 are under selection in germinal center B-cell (GCB) lymphoma patients. We provide various lines of evidence that suggest that these mutations contribute to the cancer cell survival via improving the expression levels of the anti-apoptotic BCL2 gene.