The genetic landscape of mutations in Burkitt lymphoma
- 11 November 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 44 (12), 1321-1325
- https://doi.org/10.1038/ng.2468
Abstract
Sandeep Dave and colleagues report exome sequencing of 59 Burkitt lymphomas. They report recurrent mutations in many genes, including ID3, MYC, GNA13, RET, PIK3R1, NOTCH1 and the SWI/SNF genes ARID1A and SMARCA4. Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.Keywords
This publication has 39 references indexed in Scilit:
- E and ID proteins branch outNature Reviews Immunology, 2009
- Design and analysis issues in genome-wide somatic mutation studies of cancerGenomics, 2009
- 1000 Genomes projectNature Biotechnology, 2008
- The Genomic Landscapes of Human Breast and Colorectal CancersScience, 2007
- Determinants of protein function revealed by combinatorial entropy optimizationGenome Biology, 2006
- Molecular Diagnosis of Burkitt's LymphomaThe New England Journal of Medicine, 2006
- A Biologic Definition of Burkitt's Lymphoma from Transcriptional and Genomic ProfilingThe New England Journal of Medicine, 2006
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial.1997
- Genomic alterations of the c-myc protooncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomasZeitschrift für Krebsforschung und Klinische Onkologie, 1991