Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1.
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 (~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 PRDM1-mutated), but not restricted to those cases, and lead to expression of an impaired PRDM1/Blimp1α 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/Blimp1α owing to genetic changes is responsible for the phenotype of plasmablastic lymphoma cases.
Pathology Department, Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla/IDIVAL, Santander, Spain.|Laboratorio de Genómica del Cáncer, IDIVAL, Santander, Spain.
Santiago
0000-0002-3565-8262
S
Montes-Moreno
Laboratorio de Genómica del Cáncer, IDIVAL, Santander, Spain.
Nerea
N
Martinez-Magunacelaya
Pathology Department, Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla/IDIVAL, Santander, Spain.
Tomás
T
Zecchini-Barrese
Hematology Department, Cytogenetics Unit, Hospital Universitario Marqués de Valdecilla/IDIVAL, Santander, Spain.
Sonia Gonzalez de
SG
Villambrosía
Pathology Department, Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla/IDIVAL, Santander, Spain.
Emma
E
Linares
Pathology Department, Fundación Jiménez Díaz, Madrid, Spain.
Tamara
T
Ranchal
Pathology Department, Fundación Jiménez Díaz, Madrid, Spain.
María
M
Rodriguez-Pinilla
Hematology Department, Cytogenetics Unit, Hospital Universitario Marqués de Valdecilla/IDIVAL, Santander, Spain.
Ana
A
Batlle
Laboratorio de Genómica del Cáncer, IDIVAL, Santander, Spain.
Laura
L
Cereceda-Company
Valdecilla Tumor Biobank Unit, HUMV/IDIVAL, Santander, Spain.
Jose Bernardo
JB
Revert-Arce
Laboratorio de Genómica del Cáncer, IDIVAL, Santander, Spain.
Carmen
C
Almaraz
Pathology Department, Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla/IDIVAL, Santander, Spain.|Laboratorio de Genómica del Cáncer, IDIVAL, Santander, Spain.
Miguel A
MA
Piris
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069293:Plasmablastic Lymphoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1
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