Cited by 418Protein Kinase Regulation and GTPase SignalingCancer Genomics and DiagnosticsLung Cancer Treatments and Mutations

Malignant Activation of a K- ras Oncogene in Lung Carcinoma But Not in Normal Tissue of the Same Patient

Santos, Eugenio, Martin-Zanca, Dionisio, Reddy, E. Premkumar, Pierotti, Marco A., Della Porta, Giuseppe, Barbacid, Mariano·1984·Science

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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Crossref · 10.1126/science.6695174

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33 of 33 references verified0 citation errors · 0 not checkable

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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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