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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutational activation of ras oncogenes is frequently encountered in human tumors. For unexplained reasons, K-ras mutations are predominantly found in pancreatic cancer, colorectal cancer and adeno-carcinoma of the lung, N-ras is predominantly found in a subset of acute leukemias and in myelodysplastic syndromes, while H-ras mutations are rare. In most tumors, ras mutations are not clearly associated with specific clinical or biological features, but in lung cancer, childhood lymphoblastic leukemia and possibly in myelodysplastic syndromes ras mutations may predict a poor prognosis. Accumulating evidence suggests that exposure to chemical carcinogens is responsible for many ras mutations in humans.
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PMID:ras and human tumors. 142 Nov 68

We studied activated mutations of K-ras gene in three forms of colorectal tumors, i.e., 45 specimens of colorectal adenoma (CA), 10 of 'cancer in adenoma' (CIA), and 24 of colorectal cancer (CC), and in 15 of gastric cancer (GC) as controls. Chromosome aberrations were also examined in 7 specimens of CA, 3 of CIA, 8 of CC, and 7 of GC. Mutation of K-ras Codon 12 was observed in 12 (26.7%) of the 45 specimens of CA, 6 (60.0%) of the 10 specimens of CIA, 6 (25.0%) of the 24 specimens of CC, and 1 (6.7%) of the 15 specimens of GC. In CA, its frequency increased with the degree of histological atypism. In CA and CIA, its frequency increased with the increase in short diameter. The most frequent chromosome aberration was the numerical excess of chromosome 7. Numerical deficiencies of chromosomes 17 and 18 or structural abnormalities of 17p+ and 18q+ were noted in 1 specimen each of CA and CIA, and 2 of CC. Thus, aberrations of these two chromosomes were concurrent. 5q--was observed in 1 specimen each of CA and CC. These findings were not contradictory to the multi-step carcinogenesis model of the colorectum based on the hypothesis that carcinogenesis requires activation of an oncogene by mutation accompanied by defects of several genes that might normally inhibit tumorigenesis.
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PMID:Genetic changes in multi-step development of colorectal cancer. 145 86

The aim of the present study was to examine whether the expression of growth factor genes, proto-oncogenes and carcinoembryonic antigen (CEA) gene in human colorectal cancer cell lines was related to their clinicobiological behavior. A significant variability among cell lines was detected for both insulin-like growth factor II and transforming growth factor beta gene message. Detectable levels of c-myc, Her-2, c-myb, K-ras and EGF receptor mRNA were found in most cell lines, whereas only 1/11 and 2/11 cell lines were positive for N-myc and c-sis message, respectively. N-myc expression was limited to a cell line originated from a tumor with neuroendocrine features, while high levels of K-ras message were found only in a cell line derived from a radioresistant tumor. CEA mRNA levels correlated well with the concentration of antigen in each cell line. On the basis of these results, our findings demonstrated that human colorectal cancer cell lines show heterogeneous expression of growth factor and CEA genes and proto-oncogenes; however, with the exception of K-ras, N-myc and CEA, other correlations between gene expression and the clinicobiological characteristics of these cell lines could not be demonstrated.
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PMID:Pattern of growth factor, proto-oncogene and carcinoembryonic antigen gene expression in human colorectal carcinoma cell lines. 149 47

We have used a rapid, non-radioactive and sensitive method based on allele-specific amplification using the polymerase chain reaction for the identification of K-ras mutations in archival tissues of colorectal carcinomas. Our purpose was to determine whether or not K-ras mutation provides, when present, a tumour marker throughout the natural history of the disease. We have studied 35 patients who developed recurrent cancer. In 71% of these patients a ras mutation in codons 12 or 13 was observed in the primary tumour. For each of these cases an identical ras mutation was found in the DNA from the local or distant recurrence. In the 29% of cases where no ras mutation was observed in the primary tumour, no newly acquired ras mutation appeared in the recurrent tumour. The time interval between primary tumours and recurrences varied from 3 to 60 months. Our results indicate that K-ras mutation provides a stable tumour marker throughout the natural history of colorectal cancer.
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PMID:Stability of K-ras mutations throughout the natural history of human colorectal cancer. 162 81

The inherited cancer-inducing disease familial polyposis coli (FPC) provides an excellent model not only for studying tumor progression in colorectal cancer but also for elucidating molecular mechanisms in general oncogenesis. This paper reviewed recent remarkable progresses of molecular mechanisms in colorectal tumorigenesis. This is concerned with the various kinds of genetic alterations that accumulate in the development from normal mucosa to adenoma, and then to adenocarcinoma in comparison with FPC and sporadic cases. This review included also information on the localization of FPC major gene. These observations indicate that in cases of colorectal tumorigenesis several genetic alterations may be involved, including activation of K-ras gene, deregulated expression of c-myc gene or c-fos gene and inactivation of tumor suppressor genes such as p53 and DCC genes, as well as the loss of heterozygosity. The observation suggest that adenomas will have undergone several gene or chromosome mutations before reaching to the fully malignant state. Therefore, DNA diagnosis for colorectal tumors in the clinical level may contribute to more accurate prognosis and better results for further therapy.
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PMID:[Diagnosis of colorectal cancer from DNA level]. 184 82

This report reviewed recent remarkable progresses on the cytomolecular mechanisms in colorectal carcinogenesis. Colorectal carcinoma is a good model for the study of multi-step progression, because we can obtain adenomatous polyps which are considered as a precancerous form. Furthermore, a familial syndrome, which is characterized by numerous adenomas of the colon, is available for linkage analysis. Recently, the p53 and DCC genes have been identified as candidate tumor suppressor genes on chromosome 17p and 18q respectively. In this paper, we present the multiple genetic alterations in colorectal carcinoma, including activation of K-ras gene and inactivation of tumor suppressor gene such as p53 and DCC genes as well as loss of heterozygosity and approach to the gene responsible for adenomatous polyposis coli by reverse genetics.
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PMID:[Cytomolecular aspects of colorectal carcinoma]. 184 88

It has been reported that mutations in the human ras gene family convert these genes into active oncogenes. In the present study using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the oligonucleotide hybridization assay, a total of 86 colorectal cancers were analyzed for the point mutations at codon 12 and 13 of K-ras genes. Mutations were present in 33 of the 86 colorectal cancers examined; 32 of the 33 mutations were at codon 12 of this gene and one of them was at codon 13. There was no apparent correlation between the presence of a ras gene mutation in a carcinoma and its anatomical location, level of differentiation, depth of invasion, degree of lymphnode metastasis or stage of progression, however, the high incidence of K-ras mutations was observed in early stage carcinomas (depth m and sm). This results support the concept that the point mutation of K-ras gene is early event in tumorigenesis of colorectal cancer.
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PMID:[Prevalence of K-ras gene mutations in human colorectal cancers]. 194 8

By using anti-NHK-ras and K-ras monoclonal antibodies, paraffin-embedded tissue specimens of 70 cases of colorectal cancers were immunohistologically examined. Correlation between incidence of expression of these oncogenes and either of postoperative survival rate and stage of colorectal cancer were calculated. The positive rate of anti-NHK-ras and K-ras staining were correlated with maximum diameters of tumor, staging, degree of Dukes classification and depth of invasion. Positive and negative rates of between NHK-ras and K-ras staining were well coincident. The cumulative postoperative survival rate of negative cases for anti-K-ras staining showed a significantly higher survival rate than that of the positive cases.
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PMID:[Immunohistological study for the ras oncogene products in colorectal cancer]. 225 Mar 77

Adenomatous polyposis, mainly of the colon, (APC) is a rare dominantly inherited susceptibility to colon cancer in which individuals develop hundreds of polyps mainly in their large bowel. The APC gene has been localised to chromosome 5q21 by following up a case report of an individual with an interstitial deletion on chromosome 5q who had multiple developmental abnormalities together with adenomatous polyposis. A DNA marker (D5S71) was found to be closely linked to APC in family studies and localised to 5q21 by in situ annealing. Material from further patients with deletions in this region of chromosome 5 has been used, by a combination of somatic cell hybrid and long-range DNA analysis, to identify new DNA markers close to the APC gene. These and other markers now provide the basis for genetic counselling of nearly all families with APC. These studies are being extended, together with other approaches for analysing DNA clones around the APC gene, in the search for the gene itself. Allele loss in tumour as compared to normal tissue from sporadic cases of colorectal carcinomas has clearly implicated the APC gene in at least 25 to 40% of all cases of colorectal carcinomas. Similar studies by Vogelstein and others as well as ourselves have further implicated recessive changes on chromosomes 17 and 18 in the development of colorectal carcinomas. Following the demonstration by Vogelstein of the role of p53 mutations in connection with the chromosome 17 changes, we have now shown, using monoclonal antibodies to the mutant p53 products and by other approaches, that changes in the p53 gene may occur in up to 50% or more of colorectal carcinomas. Frequent mutations of the K-ras dominant oncogene, as well as changes in the expression of human leucocyte antigen (HLA)-A, B, C determinants, are further genetic changes that appear commonly to be involved in the progression of colorectal carcinomas. The latter have important implications for T cell immune response to tumours and its manipulation for treatment and even prevention of colorectal cancer. We may soon be approaching a situation when it will become possible to identify all the genetic steps and their sequence during tumour progression, as well as their functional significance largely through the induction of inappropriate growth and the suppression of differentiation.
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PMID:Genetic analysis of colorectal cancer. 256 87

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.
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PMID:The ras gene family and human carcinogenesis. 328 42


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