title: A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma.
abstract: Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ozawa
authors.affiliation: Program in Epithelial Biology, Stanford University, Stanford, CA, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Bhaduri
authors.affiliation: Department of Laboratories, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Chisholm
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Baker
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.|Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Zehnder
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Sandra
authors.identifier: 0000-0003-0713-7651
authors.initials: S
authors.lastname: Luna-Fineman
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Link
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Merker
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ohgami
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor