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The ras gene family and human carcinogenesis
1Department of Medical Biochemistry, Sylvius Laboratories, University of Leiden, The Netherlands.
Abstract:
It has been well established that specific alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurring in either codon 12, 13 or 61 or, alternatively, a 5- to 50-fold amplification of the wild-type gene. Activated ras oncogenes have been found in a significant proportion of all tumors but the incidence varies considerably with the tumor type: it is relatively frequent (20-40%) in colorectal cancer and acute myeloid leukemia, but absent or present only rarely in, for example, breast tumors and stomach cancer. No correlation has been found, yet, between the presence of absence of an activated ras gene and the clinical or biological features of the malignancy. The activation of ras oncogenes is only one step in the multistep process of tumor formation. The presence of mutated ras genes in benign polyps of the colon indicates that activation can be an early event, possibly even the initiating event. However, it can also occur later in the course of carcinogenesis to initiate for instance the transition of a benign polyp of the colon into a malignant carcinoma or to convert a primary melanoma into a metastatic tumor. Apparently, the activation of ras genes is not an obligatory event but when it occurs it can contribute to both early and advanced stages of human carcinogenesis.
Insights
Ras gene mutations can activate oncogenes, contributing to various cancers like colorectal cancer and leukemia. These genetic alterations can occur early or late in tumor development, influencing cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ras genes (H-ras, K-ras, N-ras) can become oncogenes through specific alterations.
- These alterations include point mutations (codons 12, 13, 61) or gene amplification.
Purpose of the Study:
- To review the role of ras oncogene activation in human carcinogenesis.
- To examine the incidence and implications of ras gene alterations in different tumor types.
Main Methods:
- Literature review of studies on ras gene mutations and cancer.
- Analysis of ras oncogene incidence across various human malignancies.
Main Results:
- Activated ras oncogenes are found in a significant proportion of tumors, with varying incidence by cancer type (e.g., common in colorectal cancer, rare in breast cancer).
- Ras gene activation can be an early event in tumor formation (e.g., colon polyps) or occur later, promoting malignancy or metastasis.
- No correlation has been established between ras gene status and clinical/biological features of cancer.
Conclusions:
- Ras oncogene activation is a key event in multistep carcinogenesis, not obligatory but significant.
- Ras gene alterations contribute to both early and advanced stages of human cancer development.