ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2024
Lung-MAP Next-Generation Sequencing Analysis of Advanced Squamous Cell Lung Cancers (SWOG S1400).
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comparative survival analysis of stage T1-T2N0M0 lung squamous cell carcinoma and adenocarcinoma using SEER data, and nomogram analysis for early-stage lung squamous cell carcinoma.Translational cancer research · 2025Article
- Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions.Nature reviews. Clinical oncology · 2025Review
- Landscape of targeted therapies for lung squamous cell carcinoma.Frontiers in oncology · 2024Review
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Authors and funding
15 authors.
Funding
Abstract
introductionSquamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, that is, by next-generation sequencing (NGS), is needed to identify potential targets. Lung Cancer Master Protocol Southwest Oncology Group S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic sub-studies.
methodsTumors underwent NGS using Foundation Medicine's FoundationOne research platform, which sequenced the exons and/or introns of 313 cancer-related genes. Mutually exclusive gene set analysis and Selected Events Linked by Evolutionary Conditions across Human Tumors were performed to identify mutually exclusive and co-occurring gene alterations. Comparisons were performed with data on 495 lung SqCC downloaded from The Cancer Genome Atlas. Cox proportional hazards models were used to assess associations between genetic variants and survival.
resultsNGS data are reported for 1672 patients enrolled on S1400 between 2014 and 2019. Mutually exclusive gene set analysis identified two non-overlapping sets of mutually exclusive alterations with a false discovery rate of less than 15%: NFE2L2, KEAP1, and PARP4; and CDKN2A and RB1. PARP4, a relatively uncharacterized gene, showed three frequent mutations suggesting functional significance: 3116T>C (I1039T), 3176A>G (Q1059R), and 3509C>T (T1170I). When taken together, NFE2L2 and KEAP1 alterations were associated with poorer survival.
conclusionsAs the largest dataset to date of lung SqCC profiled on a clinical trial, the S1400 NGS dataset establishes a rich resource for biomarker discovery. Mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations suggests that PARP4 may have an uncharacterized role in a key pathway known to impact oxidative stress response and treatment resistance.
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