{
  "abstract": "Genome-scale cancer-driver discovery is limited by statistical uncertainty in driver calling and by experimental constraints on mutations available for selection. We developed 3xfOnc3 - a three-frame Sleeping Beauty (SB) mutagenesis system designed to broaden functional perturbations and reduce integration biases of traditional SB screens - and tested it in vivo in mouse liver. Within 12 months, 60% of mice developed heterogeneous hepatocellular tumors. Tumor-selected integrations were interpreted against an empirical reference from SB-based therapeutic gene delivery to hepatocytes, enabling correction for gene targetability. Background-aware filtering prioritized 315 driver candidates, including 243 protein-coding genes. Tumors were multiclonal, and identical integration-marked lineages expanded differently across lesions, supporting context-dependent clonal expansion. SB hits within young L1 subfamily members were selectively enriched in tumors. Human orthologues of candidate drivers were enriched for Cancer Gene Census genes and protein-altering pan-cancer mutations. Together, 3xfOnc3 reveals a background-corrected driver landscape linking driver selection to clonal tumor evolution and cross-species cancer relevance.",
  "abstract_shown": true,
  "affiliations": [
    "HUN-REN Biological Research Centre"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "G. Imre"
    },
    {
      "name": "A. Mates-Nagy"
    },
    {
      "name": "M. Raya"
    },
    {
      "name": "O. O. Verebi"
    },
    {
      "name": "L. Hudoba"
    },
    {
      "name": "A. Farago"
    },
    {
      "name": "D. Latinovics"
    },
    {
      "name": "R. Karkas"
    },
    {
      "name": "P. German"
    },
    {
      "name": "P. I. Kalman"
    },
    {
      "name": "E. Migh"
    },
    {
      "name": "A. Pettko-Szandtner"
    },
    {
      "name": "O. Kolacsek"
    },
    {
      "name": "A. Furedi"
    },
    {
      "name": "P. Horvath"
    },
    {
      "name": "T. Orban"
    },
    {
      "name": "I. Nagy"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Mates"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5detx5hd3w1gg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.31.763279",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763279v1.full",
  "id": "5detx5hd3w1gg",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763279v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "cancer biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763279v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5detx5hd3w1gg.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:00Z",
      "native_id": "10.64898/2026.10.31.763279",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763279v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Revamped transposon-induced hepatocellular carcinoma model reveals deep similarities of cancer-driver landscapes across mice and humans",
  "title_text": "Revamped transposon-induced hepatocellular carcinoma model reveals deep similarities of cancer-driver landscapes across mice and humans",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:16Z",
  "url": "https://research.draconitic.com/paper/5detx5hd3w1gg",
  "venue": "bioRxiv",
  "versions": []
}