{
  "abstract": "High-risk neuroblastoma remains a major clinical challenge despite intensive multimodal treatment. Alterations in the anaplastic lymphoma kinase (ALK) gene are frequent in NB and correlate with poor outcome. ALK-F1174L and ALK-R1275Q are the most prevalent activating mutations, but their specific effects on tumor behavior remain unclear. Here, we compared the impacts of ALK-wild-type (wt), ALK-F1174L and ALK-R1275Q in several NB xenograft models. In the SK-N-Be2c model, ALK-F1174L mediated numerous transcriptomic alterations without affecting tumor behavior. In GIMEN cells, only ALK-F1174L and ALK-R1275Q conferred tumorigenicity with distinct growth kinetics and transcriptional programs. In the mesenchymal SH-EP model, ALK variants induced distinct phenotypes, with ALK-wt and ALK-F1174L promoting partial transition toward neuroblastic identity. All ALK variants induced lung metastases, but with allele-specific dissemination patterns. Transcriptomic profiling of SH-EP tumors and corresponding metastases revealed partly opposing pathway regulation between ALK-F1174L and ALK-R1275Q. Overall, ALK variants differentially modulate NB behavior in a context-dependent manner.",
  "abstract_shown": true,
  "affiliations": [
    "Lausanne University Hospital and University of Lausanne"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "M. El Natour"
    },
    {
      "name": "L. Vivancos Stalin"
    },
    {
      "name": "N. Gobet"
    },
    {
      "name": "V. Praz"
    },
    {
      "name": "K. Balmas Bourloud"
    },
    {
      "name": "N. Jauquier"
    },
    {
      "name": "I. Janoueix-Lerosey"
    },
    {
      "name": "N. Riggi"
    },
    {
      "name": "R. Renella"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Muhlethaler-Mottet"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2pwavs8bdp78a.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.08.750106",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.08.750106v1.full",
  "id": "2pwavs8bdp78a",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.08.750106v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2728|Neuroblastoma Research and Treatments"
    ]
  ],
  "openalex": "W7212306009",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.08.750106v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2pwavs8bdp78a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:09Z",
      "native_id": "10.64898/2026.09.08.750106",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.08.750106v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "ALK variants Differentially Modulate Neuroblastoma Tumor Behavior and Transcriptome in a Cellular Context-Dependent Manner",
  "title_text": "ALK variants Differentially Modulate Neuroblastoma Tumor Behavior and Transcriptome in a Cellular Context-Dependent Manner",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:09Z",
  "url": "https://research.draconitic.com/paper/2pwavs8bdp78a",
  "venue": "bioRxiv",
  "versions": []
}