{
  "abstract": "Surgical decisions for intraductal papillary mucinous neoplasms (IPMNs), precursors of pancreatic cancer, depend on distinguishing low- from high-grade dysplasia, a distinction that molecular markers could refine. We microdissected 433 tumor regions from 135 patients and integrated transcriptomics, deep-learning histology, and KRAS/GNAS RNA-called variants. RNA programs and morphological motifs separated lesions by phenotype, intestinal versus others, rather than by dysplasia grade. Along gastric IPMN trajectories, low-grade lesions recapitulated the pit-chief polarity of normal gastric glands, whereas high-grade lesions were indistinguishable from pancreatobiliary lesions in morphology, RNA programs, and driver mutations. Intestinal IPMNs arose through two routes: a canonical GNAS-associated pathway and a KRAS-associated shift from low-grade gastric features, with lesions sharing driver mutations retaining common programs across phenotypes. Resolving these phenotypic trajectories clarified distinct progression paths and enabled phenotype-specific prediction of high-grade dysplasia in mucus aspirated from 94 resected lesions. These findings support a promising fluid-based assessment of IPMN status.",
  "abstract_shown": true,
  "affiliations": [
    "Universite Paris Cite, CRI, INSERM U1149"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "C. Pignolet"
    },
    {
      "name": "L. Aguilera Munoz"
    },
    {
      "name": "L. Bourlet"
    },
    {
      "name": "T. Bourega"
    },
    {
      "name": "L. Gomes"
    },
    {
      "name": "D. Mendes"
    },
    {
      "name": "N. Theou-Anton"
    },
    {
      "name": "N. Colnot"
    },
    {
      "name": "M. Albuquerque"
    },
    {
      "name": "L. de Mestier"
    },
    {
      "name": "S. Dokmak"
    },
    {
      "name": "A. Couvelard"
    },
    {
      "name": "V. Rebours"
    },
    {
      "name": "R. Nicolle"
    },
    {
      "name": "J. Cros"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5y73xer30ejs1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.757128",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757128v1.full",
  "id": "5y73xer30ejs1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757128v1",
  "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",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7220841348",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757128v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5y73xer30ejs1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:25Z",
      "native_id": "10.64898/2026.10.06.757128",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757128v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Distinct Progression Paths Underlie the Diversity of Pancreatic Papillary Cystic Neoplasms",
  "title_text": "Distinct Progression Paths Underlie the Diversity of Pancreatic Papillary Cystic Neoplasms",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:25Z",
  "url": "https://research.draconitic.com/paper/5y73xer30ejs1",
  "venue": "bioRxiv",
  "versions": []
}