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The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations—The Lung Cancer Mutation Consortium (LCMC2)
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Abstract
Purpose: Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. Experimental Design: Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC. Results: The use of targeted therapies in patients with EGFR, ERBB2, or BRAF p.V600E mutations, ALK, ROS1, or RET rearrangements, or MET amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver. Importantly, 60 patients with a history of smoking derived similar survival benefit from targeted therapy for alterations in EGFR/ALK/ROS1, when compared with 75 never smokers with the same alterations. In addition, coexisting TP53 mutations were associated with shorter survival among patients with EGFR, ALK, or ROS1 alterations. Conclusion: Patients with adenocarcinoma of the lung and an oncogenic driver mutation treated with effective targeted therapy have a longer survival, regardless of prior smoking history. Molecular testing should be performed on all individuals with lung adenocarcinomas irrespective of clinical characteristics. Routine use of massively parallel sequencing enables detection of both targetable driver alterations and tumor suppressor gene and other alterations that have potential significance for therapy selection and as predictive markers for the efficacy of treatment. Clin Cancer Res; 24(5); 1038–47. ©2017 AACR.
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“relative paucity of TP53 mutations”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [131]
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In the citing paper
“both RET and ROS1 fusion-positive LUAD are characterized by high rates of concurrent CDKN2A loss (29.8% and 30.4% for RET and ROS1-rearranged tumors respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [131]
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“both RET and ROS1 fusion-positive LUAD are characterized by high rates of concurrent CDKN2A loss (29.8% and 30.4% for RET and ROS1-rearranged tumors respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [131]
In the citing paper
“CDKN2B loss (25% and 17.7% respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [131]
In the citing paper
“CDKN2B loss (25% and 17.7% respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [131]
In the citing paper
“although the frequency of TP53 mutations appears to be somewhat higher compared to ALK-rearranged tumors (34.6%−45.5% for RET-and 45.6% for ROS1- rearranged tumors)15, 131.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [131]
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Metadata
- Authors
- Aisner, D. L., Sholl, L. M., Berry, L. D., Rossi, M. R., Chen, H., Fujimoto, J., Moreira, A. L., Ramalingam, S. S., Villaruz, L. C., Otterson, G. A., Haura, E., Politi, K., Glisson, B., Cetnar, J., Garon, E. B., Schiller, J., Waqar, S. N., Sequist, L. V., Brahmer, J., Shyr, Y., Kugler, K., Wistuba, I. I., Johnson, B. E., Minna, J. D., Kris, M. G., Bunn, P. A., & Kwiatkowski, D. J.
- Affiliations
- University of Colorado Cancer Center (US)
- Brigham and Women's Hospital (US)
- Vanderbilt-Ingram Cancer Center (US)
- Emory University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Pittsburgh (US)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- Moffitt Cancer Center (US)
- Yale University (US)
- Oregon Health & Science University (US)
- University of California, Los Angeles (US)
- The University of Texas Southwestern Medical Center (US)
- Washington University in St. Louis (US)
- Massachusetts General Hospital (US)
- Johns Hopkins University (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Aisner, Dara L.
- Kwiatkowski, David J.
- ORCID
- Aisner, Dara L.
- Sholl, Lynette M.
- Berry, Lynne D.
- Rossi, Michael R.
- Chen, Heidi
- Fujimoto, Junya
- Moreira, Andre L.
- Ramalingam, Suresh S.
- Villaruz, Liza C.
- Otterson, Gregory A.
- Haura, Eric
- Politi, Katerina
- Glisson, Bonnie
- Garon, Edward B.
- Schiller, Joan
- Waqar, Saiama N.
- Sequist, Lecia V.
- Brahmer, Julie
- Shyr, Yu
- Wistuba, Ignacio I.
- Johnson, Bruce E.
- Minna, John D.
- Kris, Mark G.
- Bunn, Paul A.
- Kwiatkowski, David J.
- Venue
- Clinical Cancer Research
- Published
- 2018-02-28
- Volume
- 24
- Issue
- 5
- Pages
- 1038-1047
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC7008001
- OpenAlex
- W2775798067
- Cited by
- 206
- References
- 54
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 24 · 2022: 23 · 2021: 32 · 2020: 38 · 2019: 29 · 2018: 26
- FWCI
- 21.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Free To Breathe
- National Cancer Institute (R01CA208403, P30CA008748, P30CA046934)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- lung adenocarcinoma, smoking history, TP53 mutation, targeted therapy, EGFR mutation, ALK rearrangement, ROS1 rearrangement, BRAF V600E mutation, MET amplification, survival, molecular testing, tumor suppressor, predictive biomarkers
- MeSH terms
- Adenocarcinoma of Lung, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, DNA Mutational Analysis, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Prognosis, Prospective Studies, Smoking, Biomarkers, Tumor, Survival Analysis, Tumor Suppressor Protein p53, Treatment Outcome, Young Adult, Molecular Targeted Therapy, High-Throughput Nucleotide Sequencing, Carcinogenesis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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