Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma

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• dc.contributor.author García Reyero, Júlia
• dc.contributor.author Martínez Magunacelaya, Nerea
• dc.contributor.author González de Villambrosía, Sonia
• dc.contributor.author Loghavi, Sanam
• dc.contributor.author Gómez Mediavilla, Ángela
• dc.contributor.author Tonda, Raúl
• dc.contributor.author Beltran, Sergi
• dc.contributor.author Gut, Marta
• dc.contributor.author Pereña González, Ainara
• dc.contributor.author d'Ámore, Emanuele
• dc.contributor.author Visco, Carlo
• dc.contributor.author Khoury, Joseph D.
• dc.contributor.author Montes-Moreno, Santiago
• dc.date.accessioned 2020-11-11T10:47:56Z
• dc.date.available 2020-11-11T10:47:56Z
• dc.date.issued 2020
• dc.description.abstract Plasmablastic lymphoma mutational profile is undescribed. Here we performed a targeted exonic NGS analysis of 30 plasmablastic lymphoma cases with a B cell lymphoma dedicated panel and FISH for the detection of MYC rearrangements. A complete phenotyping of the neoplastic and microenvironment cell populations was also performed. We have identified an enrichment in recurrent genetic events in MYC (69% with MYC translocation or amplification and 3 cases with missense point mutations), PRDM1/Blimp1 and STAT3 mutations. These gene mutations were more frequent in EBV positive disease. Other genetic events included mutations in BRAF, EP300, BCR (CD79A and CD79B), NOTCH pathway (NOTCH2, NOTCH1 and SGK1) and MYD88pL265P. Immunohistochemical analysis showed consistent MYC expression, higher in cases with MYC rearrangements together with phospho-STAT3 (Tyr705) overexpression in cases with STAT3 SH2 domain mutations. Microenvironment populations were heterogeneous and unrelated with EBV, with an enrichment of Tumor Associated Macrophages (TAM) and PD1 positive T cells. PD-L1 was expressed in all cases in the TAM population but only in 5 cases in the neoplastic cells (4 out of 14 EBV positive cases). HLA expression was absent in the majority of PBL cases. In summary, Plasmablastic lymphoma mutational profile is heterogeneous and related with EBV infection. Genetic events in MYC, STAT3 and PRDM1/Blimp1 are more frequent in EBV positive disease. An enrichment in TAM and PD1 reactive T lymphocytes is found in the microenvironment of PBL cases, that express PD-L1 in the neoplastic cells in a fraction of cases.
• dc.format.mimetype application/pdf
• dc.identifier.citation Garcia-Reyero J, Martinez Magunacelaya N, Gonzalez de Villambrosia S, Loghavi S, Gomez Mediavilla A, Tonda R, Beltran S, Gut M, Pereña Gonzalez A, d' Ámore E, Visco C, Khoury JD, Montes-Moreno S. Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma. Haematologica. 2020 Apr 9;106(4):1120-28. DOI: 10.3324/haematol.2020.251579
• dc.identifier.doi http://dx.doi.org/10.3324/haematol.2020.251579
• dc.identifier.issn 0390-6078
• dc.identifier.uri http://hdl.handle.net/10230/45721
• dc.language.iso eng
• dc.publisher Ferrata Storti Foundation
• dc.relation.ispartof Haematologica. 2020 Apr 9;106(4):1120-28
• dc.rights © 2020 Ferrata Storti Foundation. Papers in Haematologica are published under a Creative Commons license CC BY-NC-ND. According to this license, an article may be copied, displayed, distributed, republished or otherwise reused provided the reuse is not an adaptation or a modification and the integrity of the original paper is maintained. This license does not allow for any kind of commercial use of the paper. For more details, see About Haematologica.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Aggressive Non-Hodgkin's Lymphoma
• dc.subject.keyword Immune microenvironment
• dc.subject.keyword Oncogene activation
• dc.subject.keyword Plasmablastic lymphoma
• dc.subject.keyword Targeted NGS
• dc.title Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion