title: Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling.
abstract: Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5 of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, -19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198-3135, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Deffenbacher
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Warren
authors.initials: W
authors.lastname: Sanger
authors.forename: Yulei
authors.initials: Y
authors.lastname: Shen
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lachel
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lim
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
authors.forename: James
authors.initials: J
authors.lastname: Lynch
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Elaine
authors.initials: E
authors.lastname: Jaffe
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German K
authors.initials: GK
authors.lastname: Ott
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002051:Burkitt Lymphoma / Q000145:classification / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D020869:Gene Expression Profiling; D015321:Gene Rearrangement / Q000235:genetics; D023281:Genomics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D035683:MicroRNAs