{
  "abstract": "Background and purpose\n\nCo-occurring mutations in lung cancer can influence disease progression and treatment response. Understanding these patterns may refine prognostic stratification and therapeutic decisions.Patients/materials and methods\n\nWe analysed targeted sequencing data from 528 North Swedish non-small cell lung cancer (NSCLC) patients, validating findings in 2,239 global patients. Co-mutation enrichment was assessed using the Fisher's exact test with odds ratios, and survival associations were evaluated using Kaplan-Meier/log-rank analyses and Cox models.Results\n\nThe North Sweden cohort showed non-random co-mutation patterns shaped by pathway dependencies. The combination of Kirsten rat sarcoma virus oncogene homolog (KRAS) and STK11 co-mutation was significantly enriched in both North Sweden (p = 4.7 × 10-4) and globally (p = 2.5 × 10-22), with North Sweden co-mutants showing significantly worse survival compared with KRAS-only cases (p = 0.037). Epidermal growth factor receptor (EGFR)+phosphate and tensin homolog (PTEN) co-mutation was significantly associated with poorer survival in both cohorts (North Sweden: p = 0.013; World: p = 0.0013). EGFR+TP53 co-mutation trended towards poorer survival compared with EGFR alone, reaching significance globally (p = 1.4 × 10-5). Adenomatous polyposis coli (APC) and PTEN were positively enriched in North Sweden (p = 0.018), and co-mutants had worse survival than APC-only cases (p = 0.029), a pattern mirrored globally. KRAS+TP53 was a frequent co-mutation but not prognostically significant. KRAS and EGFR were strongly mutually exclusive in both cohorts.Interpretation\n\nPathway-level co-mutation interactions, rather than individual mutation burden, drive survival heterogeneity in lung cancer. Specific co-mutations, such as KRAS+STK11 and APC+PTEN, are enriched and linked to worse survival, supporting the clinical relevance of co-mutation analysis in NSCLC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden. nicholas.karlowatz@umu.se.",
    "Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.",
    "Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nicholas Karlowatz",
      "orcid": "0009-0003-9985-9850"
    },
    {
      "affs": [
        1
      ],
      "name": "Linda Köhn",
      "orcid": "0000-0002-2145-9385"
    },
    {
      "affs": [
        2
      ],
      "name": "Cedric Patthey",
      "orcid": "0000-0002-2627-9578"
    },
    {
      "affs": [
        2
      ],
      "name": "Jonas Nilsson",
      "orcid": "0000-0002-6533-0073"
    },
    {
      "affs": [
        2
      ],
      "name": "Mikael Johansson",
      "orcid": "0000-0003-4182-8923"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ekncc468162kc.bib",
  "cited_by": 0,
  "doi": "10.2340/1651-226x.2026.46330",
  "fulltext_url": "https://europepmc.org/articles/PMC13660355",
  "id": "ekncc468162kc",
  "issns": [
    "0284-186X",
    "1651-226X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42852590",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7221125942",
  "pdf_url": "https://europepmc.org/articles/PMC13660355?pdf=render",
  "pmcid": "PMC13660355",
  "pmid": "42852590",
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ekncc468162kc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42852590",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42852590"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Lung Cancer Treatments and Mutations",
      "subfield": "general"
    }
  ],
  "title": "Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.",
  "title_text": "Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/ekncc468162kc",
  "venue": "Acta oncologica (Stockholm, Sweden)",
  "versions": []
}