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Isolation of transforming sequences of two human lung carcinomas: structural and functional analysis of the activated c-K-ras oncogenes.
Open accessAbstract
Human lung tumors PR310 and PR371 maintained in nude mice contain activated c-K-ras oncogenes detectable by the ability of their DNAs to induce the morphological transformation of NIH 3T3 mouse fibroblasts. Using phage libraries constructed with DNA from NIH 3T3 mouse fibroblast transformants, we have isolated human sequences that span greater than 40 kilobase pairs of the c-K-ras oncogene. Based on the conservation of these human sequences in mouse fibroblast transformants, we conclude that the transforming ability of the oncogene activated in these tumors resides within a 43- to 46-kilobase-pair DNA region. No clear differences were observed between the structures of the PR310 and PR371 cloned oncogene sequences. Nucleotide sequence analysis in concert with DNA transfection experiments suggests that the PR371 oncogene has been activated by a single base change in the first exon, which results in the substitution of cysteine for glycine in position 12 of the predicted amino acid sequence. The genetic alteration responsible for the transforming activity of the PR310 oncogene, however, does not reside in the first exon. These results indicate that the activation of the c-K-ras oncogene in human lung cancer can occur by different mutational events.
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“KRAS G12C mutation was identified in the same year in a human lung tumour (PR371) that was propagated in nude mice [13].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [13]
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Metadata
- Authors
- Nakano, H., Yamamoto, F., Neville, C., Evans, D., Mizuno, T., & Perucho, M.
- Affiliations
- Stony Brook University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1984-01
- Volume
- 81
- Issue
- 1
- Pages
- 71-75
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC344612
- OpenAlex
- W1986093376
- Cited by
- 133
- References
- 30
- Citations by year
- 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- 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
- Keywords
- oncogene activation, lung cancer, point mutations, cysteine substitution, oncogene structure, nude mouse xenograft, mutational mechanisms
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cell Transformation, Neoplastic, Chimera, Cloning, Molecular, DNA Restriction Enzymes, DNA, Neoplasm, Humans, Lung Neoplasms, Mice, Nude, Neoplasm Transplantation, Nucleic Acid Hybridization, Oncogenes, Transplantation, Heterologous, Mice
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