{
  "abstract": "Apparent TP53 gain or loss in repeated next-generation sequencing (NGS) may reflect technical noise, spatial heterogeneity, metachronous multiple primary tumors, or true clonal evolution. This study aimed to characterize TP53 longitudinal dynamics using a transparent verification framework. We analyzed 948 patients with non-small cell lung cancer undergoing at least two tissue-based NGS tests separated by ≥120 days (all specimens ≥20% tumor-cell content). Apparent TP53 flip events underwent two-step sequential verification: molecular lineage adjudication comparing complete variant spectra of sequential specimens, followed by an empirically anchored variant allele frequency (VAF) threshold (≥5%) derived from platform re-detection characteristics. Driver background and MET amplification were exploratory outcomes. TP53 status remained stable in 824 patients (86.9%); 124 (13.1%) showed apparent gain (n=75) or loss (n=49). Lineage adjudication excluded 54 patients (5.4% of 1,002 eligible) with fully discordant driver spectra, whose apparent flip rate was three-fold higher than concordant patients (29.6% vs. 9.6%). Sequential verification identified 92 high-confidence events (64 acquisitions, 28 losses), showing no driver enrichment (EGFR 65.2% vs. 65.4% in the cohort; P>0.99). MET amplification did not differ across trajectories (high-confidence acquired vs. persistent negative: 8.9% vs. 6.3%; P=0.52). TP53 alterations are largely stable during longitudinal monitoring. Many apparent flips reflect metachronous multiple primaries or near-detection-limit noise and are identifiable by a simple sequential framework. After artifact control, TP53 dynamics show no EGFR preference, and previously suggested MET associations were not confirmed under uniform ascertainment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dan Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Deyang Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Kun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Nana Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zichen Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Nanying Che",
      "orcid": "0000-0003-4179-1737"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ada8j0sdwr8td.bib",
  "cited_by": 0,
  "doi": "10.21037/jtd-2026-2138",
  "fulltext_url": "https://europepmc.org/articles/PMC13740728",
  "id": "ada8j0sdwr8td",
  "issns": [
    "2072-1439",
    "2077-6624"
  ],
  "landing_url": "https://europepmc.org/article/MED/42996924",
  "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": [
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7223865711",
  "pdf_url": "https://europepmc.org/articles/PMC13740728?pdf=render",
  "pmcid": "PMC13740728",
  "pmid": "42996924",
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ada8j0sdwr8td.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42996924",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996924"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Lung Cancer Treatments and Mutations",
      "subfield": "general"
    }
  ],
  "title": "Longitudinal TP53 dynamics in repeated tissue-based next-generation sequencing in non-small cell lung cancer: a real-world study with molecular lineage adjudication and sequential credibility verification.",
  "title_text": "Longitudinal TP53 dynamics in repeated tissue-based next-generation sequencing in non-small cell lung cancer: a real-world study with molecular lineage adjudication and sequential credibility verification.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/ada8j0sdwr8td",
  "venue": "Journal of thoracic disease",
  "versions": []
}