The ras gene family and human carcinogenesis.
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.
Bos
J L
JL
Department of Medical Biochemistry, Sylvius Laboratories, University of Leiden, The Netherlands.
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005784:Gene Amplification; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras); D011519:Proto-Oncogenes
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)