Journal
MODERN PATHOLOGY
Volume 30, Issue 1, Pages 85-94Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2016.162
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Funding
- Ministerio de Sanidad y Consumo, Spain [PI051623, PI052800, CP06/00002]
- Asociacion Espanola contra el Cancer (AECC), Spain
- Ministerio de Ciencia e Innovacion, Spain [SAF 2008-03871]
- Ministerio de Economia y competitividad [MBAE BA15/00053]
- Ministerio de Sanidad y Consumo (RTICC), Spain
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Plasmablastic lymphoma is an uncommon aggressive non-Hodgkin B-cell lymphoma type defined as a high-grade large B-cell neoplasm with plasma cell phenotype. Genetic alterations in MYC have been found in a proportion (similar to 60%) of plasmablastic lymphoma cases and lead to MYC-protein overexpression. Here, we performed a genetic and expression profile of 36 plasmablastic lymphoma cases and demonstrate that MYC overexpression is not restricted to MYC-translocated (46%) or MYC-amplified cases (11%). Furthermore, we demonstrate that recurrent somatic mutations in PRDM1 are found in 50% of plasmablastic lymphoma cases (8 of 16 cases evaluated). These mutations target critical functional domains (PR motif, proline rich domain, acidic region, and DNA-binding Zn-finger domain) involved in the regulation of different targets such as MYC. Furthermore, these mutations are found frequently in association with MYC translocations (5 out of 9, 56% of cases with MYC translocations were PROM-mutated), but not restricted to those cases, and lead to expression of an impaired PRDM1/Blimpla protein. Our data suggest that PRDM1 mutations in plasmablastic lymphoma do not impair terminal B-cell differentiation, but contribute to the oncogenicity of MYC, usually disregulated by MYC translocation or MYC amplification. In conclusion, aberrant coexpression of MYC and PRDM1/Blimp1a owing to genetic changes is responsible for the phenotype of plasmablastic lymphoma cases.
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