Mining for mutation hotspots in the B-cell non-Hodgkin lymphomas

Non-Hodgkin lymphomas (NHLs) collectively represent the most common hematological cancer worldwide. The two most prevalent varieties, diffuse large B-cell lymphoma and follicular lymphoma, comprise around 40% and 35% of adult NHL cases, respectively, while Burkitt lymphoma comprises around 40% of cases in children. The cellular systems that commonly become deregulated in the malignant transformation of B cells have been identified for many NHLs, however a comprehensive description of mutations affecting these pathways remains incomplete. I performed a large-scale genomic analysis to investigate mutational hotspot regions from tumour sequencing data, employing tools designed to recognize distinct patterns of positive selection with rigorous manual review of candidate hotspots. Overall, this analysis has enhanced our understanding of the genetic aberrations affecting tumour-promoting pathways and curated a collection of high-confidence mutational hotspots that may aid prognosis and diagnosis as well as facilitate the classification of NHL subtypes.