Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes.
MacDonald Theresa Y.
Cronin Maureen T.
Rogena Emily Adhiambo.
Pinkney Kerice A.
Rubin Mark A.
Ribeiro Raul C.
Stephens Philip J.
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To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded 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 < .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 roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease
CitationBlood December 20, 2012 vol. 120 no. 26 5181-5184
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NYDepartment of Pathology and Cell Biology, Division of Hematopathology, Columbia University Medical Center, New YorkDepartment of Pathology, University of Nairobi, Nairobi, Kenya;