{
  "abstract": "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.",
  "abstract_shown": true,
  "affiliations": [
    "Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil",
    "MD Anderson, United States",
    "Illinois University, United States",
    "Michigan University, United States"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Guilherme CARNEIRO"
    },
    {
      "affs": [
        0
      ],
      "name": "Cadiele Oliana REICHERT"
    },
    {
      "affs": [
        0
      ],
      "name": "Hebert Fabrício CULLER"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Claudia Cadiele Oliana NOGUEIRA ZERBINI"
    },
    {
      "affs": [
        0
      ],
      "name": "Sheila Aparecida COELHO DA SIQUEIRA"
    },
    {
      "affs": [
        0
      ],
      "name": "Iberê Cauduro SOARES"
    },
    {
      "affs": [
        0
      ],
      "name": "Renata de Oliveira COSTA"
    },
    {
      "affs": [
        0
      ],
      "name": "Vanderson Cadiele Oliana ROCHA"
    },
    {
      "affs": [
        0
      ],
      "name": "Vinicius de Camargo CALEFFI"
    },
    {
      "affs": [
        1
      ],
      "name": "Mário Luiz MARQUES-PIUBELLI,"
    },
    {
      "affs": [
        0
      ],
      "name": "Nélio Cézar DE AQUINO"
    },
    {
      "affs": [
        1
      ],
      "name": "Francisco VEGA-VAQUEZ"
    },
    {
      "affs": [
        0
      ],
      "name": "Davi FERREIRA JOFRE"
    },
    {
      "affs": [
        2
      ],
      "name": "Vanessa PEREZ-SILOS,"
    },
    {
      "affs": [
        0
      ],
      "name": "Sofia CATTENA"
    },
    {
      "affs": [
        3
      ],
      "name": "Chenguang WANG"
    },
    {
      "affs": [
        3
      ],
      "name": "Ryan WILCOX"
    },
    {
      "affs": [
        2
      ],
      "name": "Carlos MURGA-ZAMALLOA"
    },
    {
      "affs": [
        0
      ],
      "name": "Juliana PEREIRA"
    },
    {
      "affs": [
        0
      ],
      "name": "Luiz Alberto DE PADUA COVAS LAGE"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ffn80516xsvyx.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107758",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926015051",
  "id": "ffn80516xsvyx",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107758",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2734|Lymphoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7223144429",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926015051/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ffn80516xsvyx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:37Z",
      "native_id": "e0b80d0b796b4d1a976000a78e8521e1",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107758"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "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",
  "title_text": "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",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:37Z",
  "url": "https://research.draconitic.com/paper/ffn80516xsvyx",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}