TET-2 mutations predict poor outcomes and are associated with unfavorable clinical-biological features in PTCL, not otherwise specified and angioimmunoblastic T-cell lymphoma in Brazilian patients

Autor(es)

de Padua Covas Lage, Luis Alberto ; Barreto, Guilherme Carneiro ; Culler, Hebert Fabricio ; Cavalcante, Jessica Billar ; de Oliveira Alves, Lucas Bassolli ; Nardinelli, Luciana ; Bendit, Israel ; Nogueira Zerbini, Maria Claudia ; Rocha, Vanderson ; Pereira, Juliana

• Tipo de documento: Artigo Científico
• Fonte: CANCER BIOMARKERS; v. 35, n. 2, p. 13-pg., 2022-01-01.

Resumo

INTRODUCTION: Nodal peripheral T-cell lymphomas [nPTCL] constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation play a central role in their pathogenesis. However, the mutational landscape involving epigenetic regulators has never been reported in Latin American patients and their prognostic impact remains controversial. PATIENTS AND METHODS: From 2000 to 2019, 59-Brazilian patients with nPTCL were eligible for screening mutations in the IDH-1, IDH-2, RHOA, TET-2 and DNMT3A genes by Sanger sequencing at Formalin-Fixed Paraffin-Embedded samples [FFPE] of diagnosis. We reported the frequency, distribution and potential prognosis of these mutations. RESULTS: With a median follow-up of 3.70 years, estimate 2-year OS and PFS were 57.1% and 49.2%, respectively. Mutations in the IDH-1 gene were not found, mutations in the IDH-2 occurred in 3.4% (2/59), RHOA in 23.7% (14/59), TET-2 in 50.8% (30/59) and DNMT3A in 62.7% (37/59). RHOA gene mutations were more frequent in PTCL, NOS and AITL (p = 0.06). Almost half of the patients had more than one mutation in concomitance, particularly RHOA-mut and TET-2-mut. Mutations in RHOA (p = 0.030) and TET-2 (p = 0.046) were associated with high-tumor burden. In the non-ALCL subgroup (PTCL, NOS and AITL) TET-2 mutations were associated with decreased 2-year PFS [HR: 2.22, p = 0.048]. Likewise with lower overall response rate [ORR] (p = 0.048) and unfavorable clinical features, as bulky disease (p = 0.012), ECOG >= 2 (p = 0.032), B-symptoms (p = 0.012), >= 2 extranodal sites compromised (p = 0.022) and high-risk Prognostic Index for T-cell lymphoma (p = 0.005). CONCLUSION: Mutations in RHOA, TET-2 and DNMT3A were frequent in Brazilian patients with nPTCL. TET-2 mutations were associated with lower ORR for CHOP-like chemotherapy, decreased PFS and unfavorable clinical-biological characteristics in non-ALCL (PTCL, NOS and AITL). Further studies using a larger cohort may validate our findings. (AU)

• Processo FAPESP: 12/50495-3 - Análise do perfil de expressão de genes de proliferação celular e resposta inflamatória e do padrão de metilação dos genes supressores tumorais p15ink4b e p16INK4A e suas implicações no prognóstico dos linfomas de células T periféricas
• Beneficiário: Juliana Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular