Recurrent RHOA mutations in pediatric B urkitt lymphoma treated according to the NHL‐BFM protocols

• Published in: Genes chromosomes & cancer 2014-11, Vol.53 (11), p.911-916
• Main Authors: Rohde, Marius, Richter, Julia, Schlesner, Matthias, Betts, Matthew J., Claviez, Alexander, Bonn, Bettina R., Zimmermann, Martin, Damm‐Welk, Christine, Russell, Robert B., Borkhardt, Arndt, Eils, Roland, Hoell, Jessica I., Szczepanowski, Monika, Oschlies, Ilske, Klapper, Wolfram, Burkhardt, Birgit, Siebert, Reiner
• Format: Article
• Language: English
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.22202

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. © 2014 Wiley Periodicals, Inc.