{
  "abstract": "Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement characterizes a subgroup of patients who show sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients. Methods: We retrospectively analyzed 96 patients with NSCLC with ALK detected by immunohistochemical staining (VENTANA anti-ALK(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of ALK fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed. Results: Among the 96 patients with immunohistochemically identified ALK fusions, 80 (83%) were confirmed by next-generation sequencing. TP53 mutation was the most commonly co-occurring mutation with ALK rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog (KRAS) G12, 1 epidermal growth factor receptor (EGFR) 19del, and 1 MET exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 (EML4)-ALK fusions were identified in 95% of ALK-rearranged patients, with 16.2% of them also harboring additional non-EML4-ALK fusions. Nineteen non-EML4 translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring PIK3R2 alterations showed a trend toward shorter progression-free survival (6 vs. 13 months, P=0.064) and significantly shorter overall survival (11 vs. 32 months, P=0.004) than did PIK3R2-wild-type patients. Patients with concomitant alterations in PI3K the signaling pathway also had a shorter median overall survival than those without such alterations (23 vs. 32 months, P=0.014), whereas progression-free survival did not differ significantly. Conclusions: The spectrum of ALK-fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "Jingjing Li"
    },
    {
      "name": "Bin Zhang"
    },
    {
      "name": "Yu Zhang"
    },
    {
      "name": "Feng Xu"
    },
    {
      "name": "Zhenfa Zhang"
    },
    {
      "name": "Lin Shao"
    },
    {
      "name": "Chunhe Yan"
    },
    {
      "name": "Paola Ulivi"
    },
    {
      "name": "Marc G Denis"
    },
    {
      "name": "Petros Christopoulos"
    },
    {
      "name": "Vincent Thomas De Montpréville"
    },
    {
      "name": "Eric H Bernicker"
    },
    {
      "name": "Anthonie J van Der Wekken"
    },
    {
      "name": "Changli Wang"
    },
    {
      "name": "Dongsheng Yue"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/94kcbxxp171cr.bib",
  "cited_by": 19,
  "doi": "10.21037/tlcr-21-160",
  "fulltext_url": null,
  "id": "94kcbxxp171cr",
  "issns": [
    "2218-6751",
    "2226-4477"
  ],
  "landing_url": "https://hal.science/hal-05753609v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W3148434193",
  "pdf_url": "https://hal.science/hal-05753609/document",
  "pmcid": null,
  "pmid": "33889527",
  "published": "2026-09-17",
  "publisher": "AME Publishing Company",
  "ris": "https://research.draconitic.com/paper/94kcbxxp171cr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:36Z",
      "native_id": "hal-05753609",
      "source": "hal",
      "url": "https://hal.science/hal-05753609v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:2730|Lung Cancer Research Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib",
  "title_text": "Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:36Z",
  "url": "https://research.draconitic.com/paper/94kcbxxp171cr",
  "venue": "Translational Lung Cancer Research",
  "versions": []
}