Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in anti-apoptotic and chromatin-remodeling genes.

To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL) we performed clinical-grade next generation sequencing (NGS) of 189 cancer-related genes on 29 formalin-fixed paraffin embedded (FFPE) primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations (p<0.0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the role of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.