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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutants of SV40 with deletions of a few to several thousand base pairs have been constructed in vitro and cloned in cultured monkey cells. The location and size of these deletions has been determined by restriction endonuclease mapping and electron microscopic and enzymatic analysis of DNA heteroduplex molecules. Analysis of the phenotype of these deletion mutants permits us to specify the locations of the known SV40 genes, in particular, the novel organization of SV40s two early genes that are required for oncogenesis.
CRC Crit Rev Biochem 1979 Nov
PMID:The physical and genetic organization of a viral genome. 22 44

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 discovery and characterization of growth regulatory genes, in the form of oncogenes, and their counterparts, tumor suppressor (TS) or antioncogenes, has vastly expanded the basic understanding of tumorigenesis. Human solid tumors, such as colorectal cancer, for which the molecular genetics have been most clearly defined, display progressive evolution from cellular dysplasia to anaplasia and metastasis through the stepwise accumulation of genetic defects, involving the regulation and expression of both oncogenes and TS genes. The study of basic genetic abnormalities in melanoma and the identification of the most fundamental of these is critical both to the understanding of abnormal melanocyte proliferation and its potential pharmacologic or immunologic regulation, and also to the identification and screening of patients at high risk for the development of melanoma. The search for such genetic abnormalities has included an analysis of melanomas for defects in known characterized oncogenes and TS genes, and, more importantly, the use of families with hereditary melanoma (HM) and dysplastic nevi in an endeavor to find the melanoma gene. The importance of HM is fundamental, since in the case of other hereditary cancer syndromes for which the genetic basis has been identified, the same or similar genetic abnormalities underlie sporadic tumors of the same tissue type. Thus HM is likely to be the major signpost to the melanomagenic defect.
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PMID:Hereditary melanoma and the search for the melanoma gene. 156 6

Colorectal tumours have proven to be an excellent system in which to identify and study the genetic alterations involved in the development of a common human neoplasm. A prevalent view is that colorectal tumours appear to arise as the result of multiple genetic alterations in the alleles of both oncogenes and tumour suppressor genes. The accumulation of genetic alterations appears to accompany the clinical and biological progression of the tumours and may determine the phenotype of the tumour cells. In addition to the many somatic alterations identified at various stages of colorectal tumour development, recent studies have led to the identification of the adenomatous polyposis coli (APC) gene, which, when mutated in the germline, predisposes to the development of colorectal tumours. On the basis of studies of inherited and somatic mutations in colorectal tumours, a genetic model for colorectal cancer development has been proposed. Although the model is undoubtedly incomplete, it nevertheless provides a useful framework for further studies of the multiple events that underlie human tumour initiation and progression. Numerous questions remain to be answered, including identification of the normal function of the genes implicated in tumorigenesis, how mutations in these genes arise and are selected for and what the relative contribution of the altered genes is to various stages of the neoplastic process. Nevertheless, an optimistic outlook is that fundamental insights into the pathogenesis of human cancer are within our reach.
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PMID:Genetic alterations underlying colorectal tumorigenesis. 163 44

Progress has continued in explicating the genetics of inherited predispositions to colorectal cancer and the molecular events that lead to tumorigenesis. New polymorphic DNA markers have been described for the presymptomatic diagnosis of familial adenomatous polyposis and a candidate gene has been characterized. Pedigree studies have suggested that there may be an inherited predisposition to many apparently nonfamilial colorectal cancers and a genetic model of tumorigenesis in common colorectal cancer has been proposed that includes the activation of dominantly acting oncogenes and the inactivation of growth suppressor genes. Two features of colorectal cancer make it a particularly good model for studying neoplasia. There are several well-defined rare inherited syndromes that predispose to the development of colorectal cancer in an autosomal dominant manner, and the majority of carcinomas are thought to arise from preexisting benign adenomatous polyps, allowing the analysis of genetic changes during tumorigenesis.
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PMID:The genetics and molecular biology of colorectal cancer. 165 4

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

Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC (mutated in colorectal cancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.
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PMID:Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. 184 68

Oncogenesis results from an accumulation of genetic mutations in a single cell. Mutations may result in the cell acquiring new functions or losing specific functions required for normal growth control. Evidence for the latter may be adduced from the results of fusing tumour and normal cells to form somatic cell hybrids, and from studies of allele loss in a number of human tumours. The locations the critical genes have been discerned in some cancer predisposition syndromes either by observations of consistent cytogenetic abnormalities, or by genetic linkage studies, or both. Genes whose inactivation is important in the genesis of retinoblastoma, Wilms' tumour and colorectal cancer have been identified and cloned. Their normal functions include control of transcription and cell-cell interactions. In the case of retinoblastoma, the interaction between the normal gene product and that of the transforming genes of a number of oncogenic DNA viruses has been delineated. Identification of 'tumour suppressor' genes has not only improved understanding of the process of oncogenesis, but may also aid in the presymptomatic detection of mutant gene carriers.
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PMID:Recessive oncogenes, antioncogenes and tumour suppression. 186 44

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

Two features of colorectal cancer have greatly aided the recent progress in understanding its genetics: firstly the majority of colorectal cancers arise from premalignant adenomatous polyps allowing the analysis of somatic genetic changes during tumorigenesis, and secondly there are several well defined inherited syndromes that predispose to colorectal cancer in an autosomal dominant manner. The familial polyposis gene has been mapped to chromosome 5q and loss of material on chromosome 5 shown in a large proportion of sporadic (non-familial) adenomas and carcinomas. Allele loss has also been found in a high proportion of colorectal cancers on chromosomes 17 and 18 and the respective genes involved identified as that coding for the oncoprotein p53 on 17p and the DCC ('deleted in colorectal carcinomas') gene on 18q. In addition activation of k-ras is found frequently in colorectal adenomas and carcinomas. The development of colorectal neoplasia is associated with the accumulation of genetic changes. Family studies of apparently sporadic colorectal cancer probands have shown an increased incidence of adenomas and carcinomas in first degree relatives. More recently pedigree studies have suggested that an inherited predisposition may be responsible for the majority of colorectal tumours.
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PMID:The genetics of colorectal cancer. 210 25


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