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

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

Abnormality of tumor suppressor gene p53 is supposed to be associated deeply with colon carcinogenesis. We have examined the aberrant expression of the p53 protein in human colorectal cancer or adenomatous tissues immunohistochemically using monoclonal antibody PAb 1801. In microwave-fixed colorectal tissues, p53 was successfully detected in more than 60% of carcinomas. Specific signal for p53 was restricted in the nuclei of cancer cells, while no staining was observed in adjacent normal mucosa. The incidence of p53 expression in colorectal carcinomas was not affected by pathological features such as tumor size, histological grade, nor depth of invasion. In about 10% of colorectal adenomas, weak signal was detected in a few adenomatous glands. Heat shock protein of 72 kDa (HSP72), known to form complex with the mutant-type of p53 in tumor cells, was also detected immunohistochemically in 25% of p53-positive cases. In these cases, high incidence of lymphnodal or distant metastasis was observed, which suggests that expression of both p53 and HSP72 may indicated biological malignancy of the colorectal carcinomas.
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PMID:[Expression of P53 and heat shock protein in colorectal tumors: an immunohistochemical study]. 194 62

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

The p53 transformation-related gene is located on 17p, a chromosomal segment frequently under-represented in colorectal adenocarcinoma karyotypes. We have developed a flow cytometric method for detection of its gene product on isolated nuclei by indirect immunofluorescence. Criteria for defining the presence of p53 were established, using parameters related to the difference of fluorescence obtained by incubating nuclei with a specific monoclonal antibody (MAB) versus isotypic control. This method allowed simultaneous quantitation of p53 and DNA in tumor nuclei to be made. Twenty-two of the 41 tumors analyzed (54%) were found to overexpress p53 when compared to 13 normal mucosa specimens. Repeated preparations from different fragments of the same tumor gave reproducible results for the 21 cases tested. p53 was detected in a higher proportion of disseminated tumors (64%) compared to localized disease (39%), but the difference did not reach statistical significance (chi 2 = 2.4, p greater than 0.10). Tumors containing aneuploid cell subpopulations were also more frequently positive (65%) than diploid ones (20%), the difference being significant (Fisher's exact test, p less than 0.03). This dual parameter flow cytometric method, evaluating both DNA ploidy and p53 expression, may prove useful in identifying different biological subgroups of colorectal cancer.
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PMID:Simultaneous monitoring of P53 protein and DNA content of colorectal adenocarcinomas by flow cytometry. 213 12

Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer. 228 1

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

The expression of oncogenes (c-myc, c-fos, c-Ki-ras, c-Ha-ras, and p53) was examined by Northern blot analysis using freshly isolated human colorectal and gastric cancers and noncancerous portions as the controls. Remarkably high levels of c-myc expression were found in colorectal cancers (eight of 11), but not in gastric cancers. High levels of c-myc expression were also detected in colorectal polyps and in metastatic liver tumors. In colorectal polyps, the transcript levels significantly correlated with the histologic malignancy and the size. In contrast, neither c-fos nor c-Ki-ras was overexpressed in colorectal and gastric cancers, and transcripts of c-Ha-ras and p53 were not evident in any tissue examined. In light of these observations the c-myc expression may be specifically associated with the evolution of colorectal cancer as well as progression and maintenance stages, hence may prove to be a useful marker to evaluate the malignant potential of colorectal polyps.
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PMID:Expression of c-myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential. 274 65

Murine strains which bear constitutive inactivating mutations of either the APC or the p53 tumor suppressor genes are characterised by spontaneous tumors. APC mutated (Min) mice develop large and small bowel adenomas, a small proportion of which, in time, become malignant. p53 deficient mice develop predominantly lymphoma and sarcoma. By interbreeding these strains we have shown that there is co-operativity between these mutations, leading to a shift in phenotype. Most notably, this was characterised by a range of abnormalities of the exocrine pancreas in 83% of animals heterozygous for the APC mutation and constitutively null for functional p53. Dysplasia and preneoplastic foci were seen in 61% of these animals and pancreatic acinar cell adenocarcinoma in 22%. Analysis of these tumors showed them to have lost the remaining wild-type copy of APC. Similar loss of APC was not associated with the development of other extra-intestinal tumors. Surprisingly, given the proposed role for loss of function mutations of the p53 gene in the development of human colorectal cancer, we have found no evidence for either an increase in the rate of adenoma formation in APC +/-, p53 -/- animals, or an increased rate of progression to malignancy compared with APC +/- p53 +/+ mice. These findings highlight striking tissue-specific differences in the tumor suppressor effects of p53.
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PMID:Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy. 747 22

We present a restriction fragment length polymorphism (RFLP) analysis of 29 benign and 30 malignant prostatic tumors, using polymorphic DNA probes to the putative tumor suppressor genes DCC (Deleted in Colorectal Carcinoma; chromosome 18q21.3), nm23-H1 (17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53 (17p13). Six of 23 evaluable cancers (26%) showed loss of heterozygosity (LOH) at DCC; 5 were advanced stage and one was clinically localized (p < 0.05). Mapping 18q deletions, another (advanced) cancer showed LOH at a locus distal to DCC (18q22), but no LOH at DCC. Three of 15 evaluable cancers (20%), all advanced, showed LOH at APC. Three of eight (38%) cancers, of which 2 were advanced, showed LOH at p53. One high grade/stage cancer of 21 (5%) showed LOH at nm23-H1 (and also at DCC). Combining data, allelic losses at either DCC, APC, or p53 genes were seen in 13% of localized cancers, but in 71% of advanced cancers (p < 0.002). Allelic loss involving nm23-H1 is rare in prostatic carcinoma. We suggest that loss of tumor suppressor genes DCC and/or an unidentified gene located distally on chromosome 18q, APC, or p53 may influence progression in prostatic carcinoma.
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PMID:Somatic allelic loss at the DCC, APC, nm23-H1 and p53 tumor suppressor gene loci in human prostatic carcinoma. 751 Mar 45


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