EPIGENETIC MUTATIONAL LANDSCAPE ASSESSED BY WHOLE-EXOME SEQUENCING REVEALS NEW DIAGNOSTIC AND PROGNOSTIC BIOMARKERS IN NODAL PERIPHERAL T-CELL LYMPHOMAS: RESULTS FROM THE INTERNATIONAL CONSORTIUM FOR PTCL STUDY

@article{carneiro2026epigenetic,
  title = {{EPIGENETIC MUTATIONAL LANDSCAPE ASSESSED BY WHOLE-EXOME SEQUENCING REVEALS NEW DIAGNOSTIC AND PROGNOSTIC BIOMARKERS IN NODAL PERIPHERAL T-CELL LYMPHOMAS: RESULTS FROM THE INTERNATIONAL CONSORTIUM FOR PTCL STUDY}},
  author = {Guilherme CARNEIRO and Cadiele Oliana REICHERT and Hebert Fabrício CULLER and Maria Claudia Cadiele Oliana NOGUEIRA ZERBINI and Sheila Aparecida COELHO DA SIQUEIRA and Iberê Cauduro SOARES and Renata de Oliveira COSTA and Vanderson Cadiele Oliana ROCHA and Vinicius de Camargo CALEFFI and Mário Luiz MARQUES-PIUBELLI, and Nélio Cézar DE AQUINO and Francisco VEGA-VAQUEZ and Davi FERREIRA JOFRE and Vanessa PEREZ-SILOS, and Sofia CATTENA and Chenguang WANG and Ryan WILCOX and Carlos MURGA-ZAMALLOA and Juliana PEREIRA and Luiz Alberto DE PADUA COVAS LAGE},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107758},
  url = {https://doi.org/10.1016/j.htct.2026.107758},
  note = {CC BY},
}

TY  - JOUR
TI  - EPIGENETIC MUTATIONAL LANDSCAPE ASSESSED BY WHOLE-EXOME SEQUENCING REVEALS NEW DIAGNOSTIC AND PROGNOSTIC BIOMARKERS IN NODAL PERIPHERAL T-CELL LYMPHOMAS: RESULTS FROM THE INTERNATIONAL CONSORTIUM FOR PTCL STUDY
AU  - Guilherme CARNEIRO
AU  - Cadiele Oliana REICHERT
AU  - Hebert Fabrício CULLER
AU  - Maria Claudia Cadiele Oliana NOGUEIRA ZERBINI
AU  - Sheila Aparecida COELHO DA SIQUEIRA
AU  - Iberê Cauduro SOARES
AU  - Renata de Oliveira COSTA
AU  - Vanderson Cadiele Oliana ROCHA
AU  - Vinicius de Camargo CALEFFI
AU  - Mário Luiz MARQUES-PIUBELLI,
AU  - Nélio Cézar DE AQUINO
AU  - Francisco VEGA-VAQUEZ
AU  - Davi FERREIRA JOFRE
AU  - Vanessa PEREZ-SILOS,
AU  - Sofia CATTENA
AU  - Chenguang WANG
AU  - Ryan WILCOX
AU  - Carlos MURGA-ZAMALLOA
AU  - Juliana PEREIRA
AU  - Luiz Alberto DE PADUA COVAS LAGE
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107758
UR  - https://doi.org/10.1016/j.htct.2026.107758
AB  - Background: Nodal peripheral T-cell lymphomas (nPTCL) are rare, aggressive lymphoid malignancies with poor prognosis and include peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), nPTCL with T-follicular helper (TFH) phenotype, and ALK-positive and ALK-negative anaplastic large cell lymphomas (ALCL). Epigenetic dysregulation is a hallmark of these neoplasms, but diagnostic overlap and prognostic heterogeneity remain major challenges. We aimed to define epigenetic molecular biomarkers for diagnostic discrimination and prognostic stratification. Methods: We performed a retrospective, multicenter translational study of 173 FFPE diagnostic nPTCL samples from an international consortium involving the University of São Paulo, University of Michigan, University of Illinois Chicago, and MD Anderson Cancer Center. Whole-exome sequencing was performed, focusing on 50 epigenetic regulatory genes. Associations between mutations and clinical variables were assessed by Fisher’s exact test, and survival impact by Cox regression. p≤0.05 was considered significant. Results: We identified 302 distinct SNVs involving 47/50 genes, with a median of two mutations per sample (range 0–8); 16.8% harbored ≥4 mutations. Most alterations affected direct epigenetic regulation/chromatin remodeling (68.1%), followed by transcription factors (14.9%), RNA splicing/processing (8.5%), and cell signaling/proliferation/apoptosis (8.5%). The most frequently mutated genes were EP300 (28.3%), NSD1 (25.7%), DNMT3A (16.8%), RHOA (16.8%), and KMT2D (13.3%). PTCL, NOS showed the greatest heterogeneity, mainly involving EP300, NSD1, DNMT3A, and KMT2D. nPTCL-TFH displayed a more cohesive pattern centered on RHOA (36.7%), DNMT3A (33.3%), and TET2 (16.7%). ALK-negative ALCL showed an intermediate profile, whereas ALK-positive ALCL had a low mutational frequency. Histotype-exclusive candidate diagnostic biomarkers included BCORL1 in nPTCL-TFH; GATA2, KDM1A, and KDM6A in ALK-negative ALCL; and ATRX, BCOR, ETV6, KDM5A, PHF6, SF3B1, SRSF2, SUZ12, TDG, and TET1 in PTCL, NOS. Mutations in CREBBP (HR 3.54), SMARCB1 (HR 2.68), BCORL1 (HR 9.26), CDH4 (HR 3.51), GATA2 (HR 1.89), KMT2C (HR 2.66), PRPF8 (HR 3.47), KDM5A (HR 7.65), and KDM6A (HR 7.65) were associated with inferior overall survival. Each additional mutation independently increased the risk of death by 19.2% (HR 1.19, 95% CI 1.035–1.373; p=0.010). RHOA p.G17V strongly correlated with TFH phenotype (p<0.001), while NSD1 p.M1998K showed an association trend with relapsed/refractory disease (p=0.08). Conclusion: This large multi-institutional WES study confirms epigenetic disruption as a central feature of nPTCL and demonstrates distinct mutational patterns across histotypes, with greater burden in non-anaplastic subtypes. Novel candidate diagnostic and prognostic biomarkers were identified, supporting improved molecular classification and risk stratification in nPTCL.
SN  - 2531-1379
SN  - 2531-1387
ER  -