Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib
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.
Related
- Efficacy and safety of neoadjuvant targeted therapy in surgically treated patients with ALK-rearranged non-small cell lung cancer
- PBPK Model-Based Prediction of Optimal Rosuvastatin Dosing with Concomitant Ticagrelor in Elderly Patients Considering ABCG2 Genetic Variant.
- Outcomes of Surgical Versus Transcatheter Mitral Valve Repair or Replacement in Patients With Myocardial Infarction and Concomitant Mitral Regurgitation: A Retrospective Analysis of Real-World Data
- Functional Trajectories Following Clinically Selected Management of Concomitant Proximal Humerus Fractures in Geriatric Hip-Fracture Patients: A Retrospective Cohort Study
- Dynamics of IDH1 Mutation and Protein Expression Between Primary and Recurrent Gliomas and Their Prognostic Significance.
BibTeX
@article{li2026concomitant,
title = {{Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib}},
author = {Jingjing Li and Bin Zhang and Yu Zhang and Feng Xu and Zhenfa Zhang and Lin Shao and Chunhe Yan and Paola Ulivi and Marc G Denis and Petros Christopoulos and Vincent Thomas De Montpréville and Eric H Bernicker and Anthonie J van Der Wekken and Changli Wang and Dongsheng Yue},
journal = {Translational Lung Cancer Research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-21-160},
url = {https://hal.science/hal-05753609v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib
AU - Jingjing Li
AU - Bin Zhang
AU - Yu Zhang
AU - Feng Xu
AU - Zhenfa Zhang
AU - Lin Shao
AU - Chunhe Yan
AU - Paola Ulivi
AU - Marc G Denis
AU - Petros Christopoulos
AU - Vincent Thomas De Montpréville
AU - Eric H Bernicker
AU - Anthonie J van Der Wekken
AU - Changli Wang
AU - Dongsheng Yue
PY - 2026
DA - 2026/09/17
JO - Translational Lung Cancer Research
DO - 10.21037/tlcr-21-160
UR - https://hal.science/hal-05753609v1
AB - 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.
SN - 2218-6751
SN - 2226-4477
ER -