Recurrent RHOA mutations in pediatric Burkitt lymphoma treated according to the NHL-BFM protocols

Genes Chromosomes Cancer. 2014 Nov;53(11):911-6. doi: 10.1002/gcc.22202. Epub 2014 Jul 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / therapeutic use
  • Burkitt Lymphoma / genetics*
  • Burkitt Lymphoma / pathology
  • Burkitt Lymphoma / therapy
  • Child
  • Child, Preschool
  • Cohort Studies
  • Daunorubicin / therapeutic use
  • Female
  • Humans
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy
  • Male
  • Mutation
  • Pediatrics
  • Prednisone / therapeutic use
  • Vincristine / therapeutic use
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • RHOA protein, human
  • Vincristine
  • Asparaginase
  • rhoA GTP-Binding Protein
  • Prednisone
  • Daunorubicin

Supplementary concepts

  • PVDA protocol