Malignant Activation of a K- ras Oncogene in Lung Carcinoma But Not in Normal Tissue of the Same Patient
Abstract
A single genetic alteration, a guanine-to-cytosine transversion, is responsible for the acquisition of malignant properties by K- ras genes of two human tumor cell lines established from carcinomas of the bladder (A1698) and lung (A2182). As a consequence, arginine instead of the normal glycine is incorporated into the K- ras -coded p21 proteins at amino acid position 12. This mutation creates a restriction enzyme polymorphism that can be used to screen human cells for transforming K- ras genes. This approach was used to identify the mutational event responsible for the malignant activation of a K- ras oncogene in a squamous cell lung carcinoma of a 66-year-old man; this point mutation was not present in either the normal bronchial or parenchymal tissue or in the blood lymphocytes. Hence, malignant activation of a ras oncogene appears to be specifically associated with the development of a human neoplasm.
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KRAS G12R point mutation was first identified in 1984 in tumour tissue of a 66-year-old man with squamous cell lung carcinoma.
“In 1984, an activating KRAS G12R point mutation was first identified in the tumour tissue of a 66-year-old man with squamous cell lung carcinoma, which was not present in normal parenchymal or lymphocytes [12].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [12]
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- Authors
- Santos, E., Martin-Zanca, D., Reddy, E. P., Pierotti, M. A., Della Porta, G., & Barbacid, M.
- Affiliations
- National Cancer Institute (US)
- Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20205.
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy
- Venue
- Science
- Published
- 1984-02-17
- Volume
- 223
- Issue
- 4637
- Pages
- 661-664
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1992409084
- Cited by
- 418
- References
- 33
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 3 · 2023: 10 · 2022: 16 · 2021: 12 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 10 · 2015: 18 · 2014: 11 · 2013: 20 · 2012: 11
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- 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
- K-ras oncogene, lung cancer, squamous cell carcinoma, point mutations, restriction enzyme polymorphism, malignant transformation, p21, cancer screening
- MeSH terms
- Base Sequence, Cell Transformation, Neoplastic, DNA, Neoplasm, Genes, Dominant, Humans, Lung Neoplasms, Mutation, Oncogenes, Organ Specificity, Polymorphism, Genetic
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