The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma
2018
Authors: Wagener R, Seufert J, Raimondi F, Bens S, Kleinheinz K, Nagel I, Altmüller J, Thiele H, Hübschmann D, Kohler CW, Nürnberg P, Au-Yeung R, Burkhardt B, Horn H, Leoncini L, Jaffe ES, Ott G, Rymkiewicz G, Schlesner M, Russell RB, Klapper W, Siebert R
CellNetworks People: Russell Robert B.
Journal: Blood. 2018 Dec 19. pii: blood-2018-07-864025. doi: 10.1182/blood-2018-07-864025

The new provisional lymphoma category Burkitt-like lymphoma with 11q aberration recently described comprises cases similar to Burkitt lymphoma (BL) on morphological, immunophenotypic and gene expression level but lacking the IG-MYC translocation. They are characterized by a peculiar imbalance pattern on chromosome 11, but the landscape of mutations is not yet described. Thus, we investigated 15 MYC-negative Burkitt-like lymphoma with 11q aberration (mnBLL,11q,) cases by copy number analysis and whole exome sequencing. We refined the regions of 11q-imbalance and identified the INO80 complex-associated gene NFRKB as positional candidate in 11q24.3. Next to recurrent gains in 12q13.11-q24.32 and 7q34-qter as well as losses in 13q32.3-q34 we identified 47 genes recurrently affected by protein-changing mutations (each >3/15 cases). Strikingly, we did not detect recurrent mutations in genes of the ID3-TCF3 axis or SWI/SNF complex that are frequently altered in BL, or in genes frequently mutated in germinal center derived B-cell lymphomas like KMT2D or CREBBP. An exception is GNA13 which was mutated in 7/15 cases. We conclude that the genomic landscape of mnBLL,11q, differs from that of BL both at the chromosomal and mutational level. Our findings implicate that mnBLL,11q, is a lymphoma category distinct from Burkitt lymphoma at the molecular level.