Mutational landscape of EGFR- , MYC- , and Kras- driven genetically engineered mouse models of lung adenocarcinoma
Open accessPublished version of a preprint
Abstract
Significance: Knowledge of oncogenic alterations that drive lung adenocarcinoma formation has enabled the development of genetically engineered mouse models that are increasingly being used to study the biology and therapeutic vulnerabilities of this disease. Given the importance of genomic alterations in these processes in human lung cancer, information on the mutational landscape of the mouse tumors is valuable for the design and interpretation of these experiments. In this study, we compared whole-exome sequencing data from lung adenocarcinomas induced by different lung adenocarcinoma-associated drivers. In contrast to their human counterparts, oncogene-driven lung adenocarcinomas in genetically engineered mouse models harbor few somatic mutations. These results have important implications for the use of these models to study tumor progression and response and resistance to therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The KL GEMM is highly resistant to anti-PD-1 therapy.
“Consistent with STK11-deficient human tumors, this lung tumor model is highly resistant to anti–PD-1 therapy (9, 19).”
From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [19]
The citation lists haven’t been fetched yet
References 52 · Cited by 194
- Authors
- McFadden, D. G., Politi, K., Bhutkar, A., Chen, F. K., Song, X., Pirun, M., Santiago, P. M., Kim-Kiselak, C., Platt, J. T., Lee, E., Hodges, E., Rosebrock, A. P., Bronson, R. T., Socci, N. D., Hannon, G. J., Jacks, T., & Varmus, H.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Yale Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Cold Spring Harbor Laboratory (US)
- Tufts University (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-10-04
- Volume
- 113
- Issue
- 42
- Pages
- E6409-E6417
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5081629
- OpenAlex
- W2529655703
- Cited by
- 194
- References
- 52
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 15 · 2023: 25 · 2022: 12 · 2021: 33 · 2020: 22 · 2019: 23 · 2018: 17 · 2017: 14 · 2016: 2
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Starr Cancer Consortium (I2-A105)
- Howard Hughes Medical Institute (030529)
- Office of Extramural Research, National Institutes of Health (K08CA160658, R01CA120247, R01CA121210, P30CA016359, P30CA008748, P50CA140146, UL1TR000457)
- Uniting Against Lung Cancer (n/a)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- lung adenocarcinoma, genetically engineered mouse models, EGFR, KRAS, c-Myc, mutation frequency, somatic mutations, clonal evolution, DNA copy number alterations, tumor evolution, driver mutations, oncogene overexpression, mutational landscape
- MeSH terms
- Exome Sequencing, Adenocarcinoma of Lung, Proto-Oncogene Mas, Adenocarcinoma, Animals, Carcinogens, Cell Transformation, Neoplastic, Disease Models, Animal, DNA Mutational Analysis, Lung Neoplasms, Mice, Transgenic, Mutation, Genes, ras, ROC Curve, Genes, myc, Point Mutation, Gene Dosage, Mice, Genome-Wide Association Study, DNA Copy Number Variations, ErbB Receptors
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
