Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas

Author(s)

Lage, Luis Alberto de Padua Covas ; Culler, Hebert Fabricio ; Barreto, Guilherme Carneiro ; Reichert, Cadiele Oliana ; Levy, Debora ; Costa, Renata de Oliveira ; Rocha, Vanderson ; Pereira, Juliana

• Document type: Journal article
• Source: CLINICAL EPIGENETICS; v. 14, n. 1, p. 8-pg., 2022-12-01.

Abstract

Nodal mature T-cell lymphomas (nMTCL) comprises a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena, including mutations in genes that control DNA methylation and histone deacetylation, in addition to inactivating mutations in the RhoA GTPase, play a central role in its pathogenesis and constitute potential new targets for therapeutic intervention. Tumor mutational burden (TMB) reflects the process of clonal evolution, predicts response to anti-cancer therapies and has emerged as a prognostic biomarker in several solid neoplasms; however, its potential prognostic impact remains unknown in nMTCL. In this study, we conducted Sanger sequencing of formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples using a target-panel to search for recurrent mutations involving the IDH-1/IDH-2, TET-2, DNMT3A and RhoA genes in 59 cases of nMTCL. For the first time, we demonstrated that high-TMB, defined by the presence of >= two mutations involving the aforementioned genes, was associated with decreased overall survival in nMTCL patients treated with CHOP-like regimens. Additionally, high-TMB was correlated with bulky disease, lower overall response rate, and higher mortality. Future studies using larger cohorts may validate our preliminary results that indicate TMB as a potential molecular biomarker associated with adverse prognosis in nMTCL. (AU)

• FAPESP's process: 12/50495-3 - Analysis of gene expression profile of cell proliferation and inflammatory response and the pattern of methylation of tumor suppressor genes p16INK4A and p15INK4b and its implications in the prognosis of peripheral T-cell lymphomas
• Grantee: Juliana Pereira
• Support Opportunities: Regular Research Grants