HEBERT FABRICIO CULLER
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Rhoa Mutation Is a Potential Biomarker Associated with Adverse Prognosis and High- Tumor Burden in Patients with Nodal Peripheral Lymphomas with T-Helper Follicular Phenotype (nPTCL-Thf): Data from a Brazilian Retrospective Cohort of Nodal PTCL(2021) LAGE, Luis Alberto de Padua Covas; BARRETO, Guilherme Carneiro; CULLER, Hebert Fabricio; CAVALCANTI, Jessica Billar; ALVES, Lucas de Oliveira; NARDINELLI, Luciana; BENDIT, Israel; ROCHA, Vanderson; PEREIRA, Juliana
- Age >= 75 Years, Clinical Stage III/IV, Neutrophilia and High Lymphocyte/Monocyte Ratio Predict Decreased Overall Survival in Elderly Patients with DLBCL, NOS Older Than 70 Years(2022) LAGE, Luis Alberto de Padua Covas; VITA, Rita Novello de; ALVES, Lucas Bassolli de Oliveira; JACOMASSI, Mayara D'Auria; CULLER, Hebert Fabricio; REICHERT, Cadiele Oliana; COSTA, Renata Oliveira; SIQUEIRA, Sheila Aparecida Coelho de; ROCHA, Vanderson; PEREIRA, Juliana
- 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(2022) LAGE, Luis Alberto de Padua Covas; BARRETO, Guilherme Carneiro; CULLER, Hebert Fabricio; CAVALCANTE, Jessica Billar; ALVES, Lucas Bassolli de Oliveira; NARDINELLI, Luciana; BENDIT, Israel; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, JulianaINTRODUCTION: 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.
- Diagnostic and prognostic implications of tumor expression of the GATA-3 gene in nodal peripheral T-cell lymphoma (nPTCL): Retrospective data from a Latin American cohort(2022) LAGE, Luis Alberto de Padua Covas; BRITO, Claudio Vinicius; LEVY, Debora; CULLER, Hebert Fabricio; COUTO, Samuel Campanelli Freitas; OLIVEIRA, Lucas Bassolli Alves de; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, JulianaBackground: Nodal peripheral T-cell lymphomas (nPTCL) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALKnegative. Their differential diagnosis and prognosis are an issue in clinical practice. Accurate biomarkers to define the different subtypes of nPTCL and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA-3 gene expression, and its capability to discriminate the different subtypes of nPTCL. Patients and methods: We retrospectively assessed GATA-3 gene expression by quantitative real time PCR (qRTPCR) from neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE) of 80 patients with nPTCL that were admitted in a single cancer treatment center from 2000 to 2017. Results: Median age was 49 years-old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years, 36.3% were classified as PTCL, NOS, 31.2% as ALK-negative ALCL, 21.2% as ALK-positive ALCL and 11.3% as AITL. The majority of cases had advanced stage cancer (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA-3 gene expression level
- GATA3 Gene - a Potential New Biomarker Associated with Adverse Outcomes in ALK1-Negative Anaplastic Large Cell Lymphoma: Preliminary Results from a Retrospective Cohort of 80 South American Cases of Nodal Peripheral T Lymphoma(2020) LAGE, Luis Alberto de Padua Covas; BRITO, Claudio Vinicius; LEVY, Debora; CULLER, Hebert Fabricio; COUTO, Samuel Campanelli Freitas; ALVES, Lucas B. O.; ZERBINI, Maria C.; ROCHA, Vanderson; PEREIRA, Juliana