title: Recurrent RHOA mutations in pediatric Burkitt lymphoma treated according to the NHL-BFM protocols.
abstract: Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in childhood. Genetically, it is characterized by the presence of an IG-MYC translocation which is supposed to be an initiating but not sufficient event in Burkitt lymphomagenesis. In a recent whole-genome sequencing study of four cases, we showed that the gene encoding the ras homolog family member A (RHOA) is recurrently mutated in pediatric BL. Here, we analyzed RHOA by Sanger sequencing in a cohort of 101 pediatric B-cell lymphoma patients treated according to Non-Hodgkin's Lymphoma Berlin-Frankfurt-Münster (NHL-BFM) study protocols. Among the 78 BLs in this series, an additional five had RHOA mutations resulting in a total incidence of 7/82 (8.5%) with c.14G>A (p.R5Q) being present in three cases. Modeling the mutational effect suggests that most of them inactivate the RHOA protein. Thus, deregulation of RHOA by mutation is a recurrent event in Burkitt lymphomagenesis in children.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Giessen, Giessen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Rohde
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: Matthias
authors.initials: M
authors.lastname: Schlesner
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Betts
authors.forename: Alexander
authors.initials: A
authors.lastname: Claviez
authors.forename: Bettina R
authors.initials: BR
authors.lastname: Bonn
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Christine
authors.initials: C
authors.lastname: Damm-Welk
authors.forename: Robert B
authors.initials: RB
authors.lastname: Russell
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Jessica I
authors.initials: JI
authors.lastname: Hoell
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.forename: Ilske
authors.initials: I
authors.lastname: Oschlies
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Birgit
authors.initials: B
authors.lastname: Burkhardt
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D009154:Mutation; D010372:Pediatrics; D011241:Prednisone / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use; D020742:rhoA GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C066737:RHOA protein, human; D014750:Vincristine; D001215:Asparaginase; D020742:rhoA GTP-Binding Protein; D011241:Prednisone; D003630:Daunorubicin