{
  "abstract": "Introduction: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic tumor predisposition syndrome. NF1 patients display remarkable phenotypic variability, even within families carrying the same NF1 mutation. With few exceptions, the identification of specific genotype-phenotype correlations has remained elusive.\n\nMethods: We utilized RNA-sequencing, whole exome sequencing data and direct DNA sequencing to determine HLA genotypes for individuals with NF1-associated high-grade glioma (HGG, n=38), low-grade glioma (LGG, n=91), and malignant peripheral nerve sheath tumors (MPNST, n=105). Odds ratios (OR), binomial p-values and false discovery values were calculated by comparing observed carrier frequencies against expected frequencies derived from ethnicity-matched population data.\n\nResults: We find that specific HLA class I and II alleles are associated with different NF1 tumor types. For example, HLA-B*40:02 is significantly associated with NF1-MPNST (OR=3.71, p=0.001, Q=0.023), increasing the lifetime risks for MPNST from 10-15.8% to about 36.6% (CI 16.1-57.2%).\n\nDiscussion: The relative cancer risk for an individual in the general population carrying a risk allele can be high, however, that individual's absolute risk for cancer typically remains very low. In contrast, individuals that carry a risk allele and are also burdened with a tumor predisposition syndrome will have a substantially higher absolute risk to develop a tumor, simply because they start at a higher baseline susceptibility for tumors. The identification of HLA-risk alleles for NF1 tumor development has the potential to improve clinical care and outcomes by prompting risk-adapted screening and treatment. It is important to note that the associations found in this study require validation in an independent prospective cohort.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, Division of Oncology, Children’s Hospital of Philadelphia",
    "Department of Pediatrics, University of Pennsylvania Perelman School of Medicine",
    "Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania",
    "Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania",
    "Departament de Fonaments Clínics, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB)",
    "Centro de Investigación Biomédica en Red de Cáncer (CIBERONC)",
    "Center for Cancer and Immunology Research, Children’s National Hospital",
    "Department of Pediatrics, The George Washington University School of Medicine and Health Sciences",
    "Translational Genomics and Bioinformatics of Cancer, Germans Trias i Pujol Research Institute (IGTP)",
    "Hereditary Cancer Group, Germans Trias i Pujol Research Institute (IGTP)"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
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        0,
        1,
        2,
        3
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      "name": "Jonathan H. Sussman"
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        0,
        1
      ],
      "name": "Stephanie N. Brosius"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Bernat Gel"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Peiyao Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alvin Farrel"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Jo Lynne Rokita"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Eduard Serra"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kai Tan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Michael J. Fisher"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "John M. Maris"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Thomas De Raedt"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fhmqgydwh4q5c.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1966259",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724378/?tool=EBI",
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  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1966259/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
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  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
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  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1966259/pdf",
  "pmcid": "PMC13724378",
  "pmid": "42973577",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fhmqgydwh4q5c.ris",
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      "origin": "openalex:2728|Neurofibromatosis and Schwannoma Cases",
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  "title": "Human leucocyte antigen class I and II alleles are associated with tumor susceptibility in neurofibromatosis type 1",
  "title_text": "Human leucocyte antigen class I and II alleles are associated with tumor susceptibility in neurofibromatosis type 1",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:21:09Z",
  "url": "https://research.draconitic.com/paper/fhmqgydwh4q5c",
  "venue": "Frontiers in Immunology",
  "versions": []
}