The genetic landscape of mutations in Burkitt lymphoma

Cassandra Love,1 Zhen Sun,1 Dereje Jima,1 Guojie Li,1 Jenny Zhang,1 Rodney Miles,2 Kristy L Richards,3 Cherie H Dunphy,3 William W L Choi,4 Gopesh Srivastava,4 Patricia L Lugar,5, 6 David A Rizzieri,5, 6 Anand S Lagoo,5, 6 Leon Bernal-Mizrachi,7 Karen P Mann,7 Christopher R Flowers,7 Kikkeri N Naresh,8 Andrew M Evens,9 Amy Chadburn,10 Leo I Gordon,10 Magdalena B Czader,11 Javed I Gill,12 Eric D Hsi,13 Adrienne Greenough,1 Andrea B Moffitt,1 Matthew McKinney,1, 5, 6 Anjishnu Banerjee,14 Vladimir Grubor,1 Shawn Levy,15 David B Dunson14 & Sandeep S Dave1, 5, 6 et al.

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.

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