Journal
GENES CHROMOSOMES & CANCER
Volume 53, Issue 11, Pages 911-916Publisher
WILEY-BLACKWELL
DOI: 10.1002/gcc.22202
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Funding
- ICGC MMML-Seq Project [01KU1002A, 01KU1002B, 01KU1002C, 01KU1002D, 01KU1002E, 01KU1002F, 01KU1002G, 01KU1002H, 01KU1002I, 01KU1002J]
- MMML-MYC-SYS [0316166B]
- German Federal Ministry of Education and Research in Germany (BMBF)
- Forschungshilfe Peiper
- Dr. Werner Jackstudt Foundation [S134 - 10.100]
- KinderKrebsInitiative Buchholz/Holm-Seppensen
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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-Munster (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. (c) 2014 Wiley Periodicals, Inc.
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