ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
ATM Mutations Associate with Distinct Co-Mutational Patterns and Therapeutic Vulnerabilities in NSCLC.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Ataxia-Telangiectasia, DNA Repair Deficits, Immune Dysfunction, and Cancer: A Review of Mechanisms, Clinical Presentations, and Emerging Therapies.Clinical reviews in allergy & immunology · 2026Review
- Review
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- Translating tumor epigenetic subtyping into methylome network-based prognostic models in early-stage NSCLC: results from the prospective MOBIT study.Journal of translational medicine · 2026Article
- Clinically relevant somatic variants and genomic discordance between primary tumors and mediastinal lymph nodes in lung adenocarcinoma.Therapeutic advances in medical oncology · 2026Article
- Advances in Computational Drug Repurposing, Driver Genes, and Therapeutics in Lung Adenocarcinoma.Biomolecules · 2025Review
- Personalizing cancer therapy: the role of pharmacogenetics in overcoming drug resistance and toxicity.Molecular biology reports · 2025Review
- Detecting likely germline variants during tumor-based molecular profiling.The Journal of clinical investigation · 2025Review
- Review
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- Over Two Years of Sustained Remission With Olaparib Monotherapy in Stage IV Non-Small Cell Lung Cancer With ATM Mutation: A Case Report.Cancer reports (Hoboken, N.J.) · 2025Article
- Dissecting the METTL3/STC2 axis in colorectal cancer: implications for drug resistance and metastasis.Cell biology and toxicology · 2025Article
- The Prognostic and Predictive Roles of Ataxia-Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy.Diagnostics (Basel, Switzerland) · 2025Article
- Novel immune checkpoint inhibitor strategies in advanced non-small cell lung cancer: towards biomarker-driven therapies?Translational lung cancer research · 2025Article
- Targeting the PD-1/PD-L1 Signaling Pathway for Cancer Therapy: Focus on Biomarkers.International journal of molecular sciences · 2025Review
- SMR-guided molecular subtyping and machine learning model reveals novel prognostic biomarkers and therapeutic targets in non-small cell lung adenocarcinoma.Scientific reports · 2025Article
- RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms.Journal of hematology & oncology · 2024Review
- Article
- PARP inhibitor synthetic lethality in ATM biallelic mutant cancer cell lines is associated with BRCA1/2 and RAD51 downregulation.Frontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 3 countries.
Funding
Abstract
purposeAtaxia-telangiectasia mutated (ATM) is the most frequently mutated DNA damage repair gene in non-small cell lung cancer (NSCLC). However, the molecular correlates of ATM mutations and their clinical implications have not been fully elucidated. EXPERIMENTAL
designClinicopathologic and genomic data from 26,587 patients with NSCLC from MD Anderson, public databases, and a de-identified nationwide (US-based) NSCLC clinicogenomic database (CGDB) were used to assess the co-mutation landscape, protein expression, and mutational processes in ATM-mutant tumors. We used the CGDB to evaluate ATM-associated outcomes in patients treated with immune checkpoint inhibitors (ICI) with or without chemotherapy, and assessed the effect of ATM loss on STING signaling and chemotherapy sensitivity in preclinical models.
resultsNonsynonymous mutations in ATM were observed in 11.2% of samples (2,980/26,587) and were significantly associated with mutations in KRAS, but mutually exclusive with EGFR (q < 0.1). KRAS mutational status constrained the ATM co-mutation landscape, with strong mutual exclusivity with TP53 and KEAP1 within KRAS-mutated samples. Those ATM mutations that co-occurred with TP53 were more likely to be missense mutations and associate with high mutational burden, suggestive of non-functional passenger mutations. In the CGDB cohort, dysfunctional ATM mutations associated with improved OS only in patients treated with ICI-chemotherapy, and not ICI alone. In vitro analyses demonstrated enhanced upregulation of STING signaling in ATM knockout cells with the addition of chemotherapy.
conclusionsATM mutations define a distinct subset of NSCLC associated with KRAS mutations, increased TMB, decreased TP53 and EGFR co-occurrence, and potential increased sensitivity to ICIs in the context of DNA-damaging chemotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.