title: Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes.
abstract: 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.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. giulinol@mskcc.org
authors.forename: Lisa
authors.initials: L
authors.lastname: Giulino-Roth
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.forename: Yifang
authors.initials: Y
authors.lastname: Tam
authors.forename: Maureen T
authors.initials: MT
authors.lastname: Cronin
authors.forename: Gary
authors.initials: G
authors.lastname: Palmer
authors.forename: Norma
authors.initials: N
authors.lastname: Lucena-Silva
authors.forename: Francisco
authors.initials: F
authors.lastname: Pedrosa
authors.forename: Marcia
authors.initials: M
authors.lastname: Pedrosa
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Emily
authors.initials: E
authors.lastname: Rogena
authors.forename: Kerice A
authors.initials: KA
authors.lastname: Pinkney
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D042002:Chromatin Assembly and Disassembly / Q000235:genetics* / Q000502:physiology; D005787:Gene Frequency; D052138:Genes, Neoplasm / Q000235:genetics; D016678:Genome / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D007223:Infant; D009154:Mutation / Q000502:physiology; D017422:Sequence Analysis, DNA / Q000379:methods*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins