Actividad Investigadora
Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1
Fecha de publicación:
Fecha Ahead of Print:
Autores de IDIVAL
Autores ajenos al IDIVAL
- Zecchini-Barrese, T
- Linares, E
- Ranchal, T
- Rodriguez-Pinilla, M
Unidades
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 0893-3952, 1530-0285
- Tipo:
- Article
- Páginas:
- 85-94
- PubMed:
- 27687004
- Enlace a otro recurso:
- www.sciencedirect.com
MODERN PATHOLOGY NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 63
Documentos
- No hay documentos
