{
  "abstract": "Background\n\nVon Hippel-Lindau (VHL) syndrome is a rare autosomal dominant multisystem tumour syndrome caused by germline VHL mutations. The traditional classification of VHL syndrome, which is largely based on pheochromocytoma penetrance, is insufficient for individualised surveillance and management. This study aimed to improve mutation-specific risk stratification and define genotype-phenotype correlations of recurrent hotspot mutations in a large Chinese cohort.Methods\n\nThis retrospective single-centre study included 674 patients with VHL disease from 283 unrelated families. Four recurrent hotspot mutation subtypes were analysed: codon 65 missense mutations, exon 2 deletion, c.481C > T, and c.224_226del. Kaplan-Meier analysis and univariate and multivariate Cox regression models were used to assess age-related tumour risks and survival outcomes.Results\n\nCodon 65 missense mutations were associated with a lower risk of retinal angioma and pheochromocytoma, indicating a relatively mild phenotype. Exon 2 deletion was characterised by a higher prevalence, earlier onset, and increased age-related risk of retinal angioma and worse renal cell carcinoma (RCC)-specific survival. Increased prevalences and age-related risks of central nervous system hemangioblastoma (CHB), RCC, and pancreatic cysts or tumours were associated with c.481C > T mutations. The c.224_226del subtype showed a distinct CHB-predominant phenotype, with higher CHB incidence, earlier onset, lower pancreatic lesion risk, and higher overall mortality.Conclusion\n\nRecurrent hotspot VHL mutation subtypes were associated with distinct clinical phenotypes and prognostic patterns. Mutation subtype-based classification (covering 19.6% of patients with VHL syndrome) may provide more precise guidance for surveillance, clinical decision-making, and genetic counselling than traditional broad classification models.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, Peking University First Hospital, Beijing, 100034, China.",
    "Institute of Urology, Peking University, Beijing, 100034, China.",
    "Beijing Key Laboratory of Precision Medicine and Innovative Translation for Urogenital Diseases, Beijing, 100034, China.",
    "National Urological Cancer Center, Beijing, 100034, China.",
    "Department of Urology, Peking University First Hospital, Beijing, 100034, China. zhjc1021@126.com.",
    "Institute of Urology, Peking University, Beijing, 100034, China. zhjc1021@126.com.",
    "Beijing Key Laboratory of Precision Medicine and Innovative Translation for Urogenital Diseases, Beijing, 100034, China. zhjc1021@126.com.",
    "National Urological Cancer Center, Beijing, 100034, China. zhjc1021@126.com.",
    "Department of Central Laboratory, Peking University First Hospital, Beijing, China. yizhouwang@bjmu.edu.cn.",
    "Department of Urology, Peking University First Hospital, Beijing, 100034, China. kan.gong@bjmu.edu.cn.",
    "Institute of Urology, Peking University, Beijing, 100034, China. kan.gong@bjmu.edu.cn.",
    "Beijing Key Laboratory of Precision Medicine and Innovative Translation for Urogenital Diseases, Beijing, 100034, China. kan.gong@bjmu.edu.cn.",
    "National Urological Cancer Center, Beijing, 100034, China. kan.gong@bjmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Chuandong Wang"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jianhui Qiu"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Tao Liu"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yuhang Bao"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Jingcheng Zhou"
    },
    {
      "affs": [
        8
      ],
      "name": "Yizhou Wang"
    },
    {
      "affs": [
        9,
        10,
        11,
        12
      ],
      "name": "Kan Gong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6w25wc8hftga3.bib",
  "cited_by": 0,
  "doi": "10.1007/s00432-026-06564-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13724643",
  "id": "6w25wc8hftga3",
  "issns": [
    "0171-5216",
    "1432-1335"
  ],
  "landing_url": "https://europepmc.org/article/MED/42967954",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2730|Ear and Head Tumors"
    ]
  ],
  "openalex": "W7172401607",
  "pdf_url": "https://europepmc.org/articles/PMC13724643?pdf=render",
  "pmcid": "PMC13724643",
  "pmid": "42967954",
  "published": "2026-08-04",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/6w25wc8hftga3.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:54Z",
      "native_id": "MED:42967954",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42967954"
    },
    {
      "first_seen": "2026-11-04T12:23:11Z",
      "native_id": "PMC13724643",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00432-026-06564-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Ear and Head Tumors",
      "subfield": "oncology"
    }
  ],
  "title": "Hotspot mutations and tumour spectrum in von Hippel-Lindau syndrome: genotype-phenotype analysis of a large Chinese cohort.",
  "title_text": "Hotspot mutations and tumour spectrum in von Hippel-Lindau syndrome: genotype-phenotype analysis of a large Chinese cohort.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T03:20:56Z",
  "url": "https://research.draconitic.com/paper/6w25wc8hftga3",
  "venue": "Journal of cancer research and clinical oncology",
  "versions": []
}