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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in understanding the molecular etiology of colorectal carcinoma have made possible a discussion of molecular targets for therapy of the disease. The genes for two inherited predispositions, familial adenomatous polyposis and the Lynch syndrome, have been mapped to specific chromosomal locations. At least five of the genes that are altered in structure or expression to give rise to the tumorigenic phenotype have been isolated by molecular cloning: The K-ras and N-ras protooncogenes have been shown to be altered by point mutation, and expression of the c-myc protooncogene is deregulated. The p53 and DCC genes, both tumor suppressor genes or antioncogenes, are deleted or altered so as to be rendered nonfunctional. Although a single tumor may not suffer all these changes, available evidence indicates that most colorectal tumors contain at least one of these alterations. In addition, work in cell culture and animal systems indicates that tumor cells may be converted to nonmalignant cells by reversing the effects of just one of these changes.
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PMID:Are there molecular targets for therapy of colon cancer? 166 28

The development of effective screening tests for colorectal tumors is essential given the high frequency of these cancers in the general population, and more especially in various groups at risk. Sporadic and hereditary colorectal cancers result from the accumulation of mutations in oncogenes, such as ras, myc, neu/HER2, and in tumor suppressor genes such as apc, dcc, p53. The detection of ras or p53 mutations in DNA extracted from stool has been shown to be feasible and might be useful for the development of new screening tests. Many mutations in these genes can also be used as new prognostic factors. Identification of mutation in the apc gene responsible for familial polyposis, or its indirect detection through the study of polymorphism in such families, is completely changing the previously recommended medical attitude for the screening of this disease, and therefore may decrease or even avoid major medical follow-up. These changes are also true for the nonpolyposis hereditary colorectal tumors, also called Lynch syndrome, since the responsible hMSH2, hMLH1, hPMS1 and hPMS2 genes have recently been cloned. Mutations in these genes do not seem to be limited to families with Lynch syndrome, and could account for a predisposition of some patients to develop colorectal or other tumors.
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PMID:Contribution of molecular oncology in the detection of colorectal carcinomas. 749 39

Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters (such as localisation, prevalence in different countries and age groups, association with HNPCC and inflammatory processes) and genetic alterations (e.g. frequency of mutation in Ki-ras and p53 genes, level of MUC2 expression) differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group.
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PMID:Is mucinous carcinoma of the colorectum a distinct genetic entity? 851 44

Molecular genetics is a tool that can be learned as a language to assist clinicians in the management of colorectal cancer patients. Following a brief review of the genetic controls of colorectal cancer, the author focuses on the models of the Registry for Familial Adenomatous Polyposis and the Registry for Hereditary Nonpolyposis Colon Cancer to demonstrate most vividly the impact molecular genetics is currently having on the practical management of colon cancer. Recent discoveries of K-ras oncogene mutations in stool cultures and the prognostic implications of mutations of the TP53 and DCC genes are discussed in the context of future applications to the management of patients.
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PMID:Contributions of molecular genetics to the clinical management of colorectal cancer. 855 21

Oncogene is not categorized as a tumor marker in a strict sense, however, cancer related oncogens play an important role as a biomarker in hereditary malignant tumors in a wide sense. Various suppressor oncogenes have been identified in the autosomal dominant hereditary diseases such as APC, in familial adenomatous polyposis, p53 in Li-Fraumeni syndrome and BRACA 1 and 2 in breast cancer. By identifying the mutation site or deletions of germ line, it is possible to make a presymptomatic diagnosis of those hereditary malignant tumors. There is splendid progress in understanding of DNA repair mechanism. Recently, the mismatch repair genes were cloned as a causing gene of HNPCC. There are another group of genes called nucleotide excision repair genes which are causative genes of various autosomal recessive hereditary diseases such as xeroderama pigmentation. Pro and cons of presymptomatic diagnosis of familial adenomatous polyposis were discussed in a series of 72 patients among 42 family trees.
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PMID:[Role of tumor marker in the presymptomatic diagnosis of hereditary malignant tumors]. 869 15

The three known mechanisms of cellular transformation and oncogenesis include mutations in proto-oncogenes, inactivation of both copies of a tumor suppressor gene, and defects in DNA mismatch repair genes. Examples of each are included to substantiate the importance of understanding these mechanisms. RET is a proto-oncogene that is fundamental to the pathogenesis, and in the current era, molecular diagnosis of MEN 2 syndromes. TP53 is a tumor suppressor gene that is mutated in individuals with Li-Fraumeni syndrome. CDKN2 is a tumor suppressor gene that is mutated in pancreatic cancers and is associated with a poorer prognosis and the development of melanoma. MSH2 is a mismatch repair gene that is important in the pathogenesis of HNPCC and Muir-Torre syndrome. Altered gene function such as loss of DCC in colon cancers may affect cell adhesion properties and promote metastases. As we begin to better define and understand the mechanisms of neoplasia, we will be able to improve current diagnosis and treatment.
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PMID:Advances in molecular genetics. 904 82

Ovarian cancer has been described in association with three autosomal dominant syndromes: familial site-specific ovarian cancer, familial breast and ovarian cancer, and the hereditary nonpolyposis colon cancer syndrome. It appears that most breast-ovarian and site-specific ovarian cancer families are explained by mutations in the BRCA1 tumor suppressor gene. Other genes associated with inherited susceptibility to ovarian cancer include BRCA2, p53, and the DNA mismatch repair genes.
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PMID:Hereditary ovarian cancer. 909 Apr 74

Recent advances in molecular biology have revealed that the alteration of multiple genes, eg., APC, K-ras, p53, DCC, are involved in multistep colorectal carcinogenesis. Some of these alterations can be used as molecular markers in genetic diagnosis. Genetic diagnoses for colorectal cancer are classified into three categories, eg., 1. identification of the career in the family of patient with hereditary disease such as FPC (Familial Polyposis Coli) or HNPCC (Hereditary Non-Polyposis Colorectal Cancer), 2. early diagnosis of colorectal cancer by identifying gene mutations in the stool, 3. assist for histopathological diagnosis, or risk assessment of the metastasis, recurrence or secondary cancer by molecular means. However, there are several problems in these genetic diagnoses. These consist of two categories, eg., 1. problems in the method of gene analyses or assay system and 2. problems in performing genetic diagnoses itself. The former includes the problem of contamination of different tissue, false positive or negative result in PCR-based analyses, heterogeneity of gene mutation in tumor tissue, and the latter includes the social, ethical or economical problems mainly related to the genetic diagnosis for hereditary colorectal cancers. In this paper, we describe the possibility of genetic diagnosis for colorectal cancers and the current problems, especially from the molecular pathological aspect, in genetic diagnosis.
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PMID:[Molecular-pathological problems of genetic diagnosis for colorectal cancer]. 910 43

Epidemiological evidence suggests that a high meat consumption and/or animal fat intake may increase the risk of colorectal cancer. The objective of this study is to examine the role of dietary factors, in particular meat preparation and consumption, in relation to colorectal adenomas, the pattern of DNA-mutations (e.g. K-ras and p53), and genetic susceptibility (NAT2, HNPCC). In a case control study on diet and colorectal adenomas (sporadic and HNPCC), acetylator status (NAT2) of cases and controls as well as K-ras and p53 mutations in adenomas will be assessed. Consumption and preparation of meat, the primary interest of this study, will be assessed by a food frequency questionnaire designed especially for this purpose.
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PMID:Meat consumption and preparation, and genetic susceptibility in relation to colorectal adenomas. 910 18

Turcot syndrome is characterized by an association of malignant brain tumors and colon cancer developing in the patient's teens. Since the mechanism of carcinogenesis in Turcot syndrome is still unclear, we analysed genetic changes in tumors from a Turcot patient with no family history of the condition. All tumors, including one astrocytoma, three colon carcinomas, and two colon adenomas, exhibited severe replication error (RER), and all colon tumors showed somatic mutations at repeated regions of TGFbetaRII, E2F-4, hMSH3, and/or hMSH6 genes. Somatic APC mutations were detected in three of three colon carcinomas, and somatic p53 mutations were detected in the astrocytoma and two of three colon carcinomas, both of which showed two mutations without allele loss. We also found that normal colon mucosa, normal skin fibroblasts and normal brain tissue from this patient showed respective high frequencies of RER, in contrast to usual HNPCC patients in which RER was very rare in normal tissues. These results suggest that extreme DNA instability in normal tissues causes the early development of multiple cancer in Turcot syndrome. A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. Additional unknown germline mutation may contribute to the genetic instability in normal tissues.
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PMID:Drastic genetic instability of tumors and normal tissues in Turcot syndrome. 941 79


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