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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.
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PMID:[Molecular analysis of breast cancers: recent developments]. 130 32

Using monoclonal antibodies, we have identified a series of tumor-associated antigens selectively expressed on tumor subtypes with distinct clinical behaviours. The mucinous antigen M344 and the gp200 surface antigen 19A211 are preferentially expressed on papillary superficial tumors and carcinoma in situ lesions of the bladder. The combination of these two antigenic markers in immunocytology and flow cytometry studies of exfoliated cells has improved the sensitivity of detection for bladder tumors. Moreover, the detection of M344- and 19A211-positive exfoliated cells from previously treated but currently tumor-free patients appears to be predictive of tumor recurrence on follow-up. These results, as well as results of bladder mapping studies in tumor patients, suggest that these antigenic changes occur in a premalignant stage and may provide tools to monitor the efficacy of chemopreventive measures. Other markers, such as the surface antigen T138 and the soluble molecules autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF), are produced by primary or recurrent tumors with a higher metastatic potential. They may be useful in identifying high risk patients for distant failure. The highly restricted antigen 19A211 is also expressed on cervix condylomas and carcinoma. This observation led us to investigate a possible viral etiology of some bladder cancers. Using PCR techniques, we detected the presence of human papillomavirus (HPV) 16 DNA sequences in a significant proportion of bladder tumors. HPV positivity was inversely correlated with the presence of p53 mutations in exons 5-9 of the same tumors as measured by PCR-SSCP technique. This combination of markers may provide a basis for chemoprevention strategies targeted to distinct etiological events.
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PMID:Strategies of chemoprevention based on antigenic and molecular markers of early and premalignant lesions of the bladder. 130 95

The authors investigated methods for analysis of oncogenes and tumor suppressor genes in lung cancers and bronchial lesions from high risk patients (retired poison gas factory workers). Amplifications of C-, L-, N-myc, length of terminal repeat array (TRA), mutations of p53 gene, p53 mRNA and K-ras genes were analysed in frozen specimens of surgically resected lung cancers. Various lesions including dysplasia, squamous metaplasia, goblet cell metaplasia, and basal cell hyperplasia were detected in the bronchial epithelium of biopsied specimens from retired poison gas factory workers. Analysis of p53 gene and k-ras gene mutations was performed on these formalin fixed, paraffin embedded samples, but no evidence of mutation has been found to date.
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PMID:[Analysis of oncogenes and suppressor genes in lung cancer and bronchial lesions from high risk group]. 130 37

In this study, structural changes of the p53 gene in primary specimens of human colorectal carcinomas were analyzed by polymerase chain reaction mediated-DNA sequencing method. Point mutations of p53 gene, including an intronic mutation case, were detected in 8 of 14 carcinomas (57%). Point mutations of the gene were also observed in 2 of 2 adenomas, suggesting that mutations occur prior to the carcinoma stage. These results support that p53 gene plays an important role in the development of colorectal cancer. The frequency of Ki-ras oncogene mutations was also studied by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP). This resulted in the rate of 42% (10/24), a quite similar value obtained by other methods. As PCR-SSCP analysis is a convenient method to detect point mutation, we have now examined 24 colorectal cancers for the p53 gene by this method, and detected the mutations. Furthermore, expression of the DCC gene, a candidate of tumor suppressor gene involved in colorectal carcinogenesis, was examined by reverse transcriptase-mediated PCR (RT-PCR) assay, resulting in significant reduction on the DCC expression in 8 of 14 carcinoma cases (57%).
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PMID:Mutations of the p53 gene and other genes involving in human colorectal carcinogenesis. 130 99

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.
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PMID:p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. 131 70

Stable interactions between simian virus 40 large T antigen and host proteins are believed to play a major role in the ability of the viral protein to transform cells in culture and induce tumors in vivo. Two of these host proteins, the retinoblastoma susceptibility protein (pRB) and p53, are products of tumor suppressor genes, suggesting that T antigen exerts at least a portion of its transforming activity by complexing with and inactivating the function of these proteins. While analyzing T antigen-host protein complexes in mouse cells, we noted a protein of 185 kDa (p185) which specifically coimmunoprecipitates with T antigen. Coimmunoprecipitation results from the formation of stable complexes between T antigen and p185. Complex formation is independent of the interactions of T antigen with pRB, p120, and p53. Furthermore, analysis of T-antigen mutants suggests that T antigen-p185 complex formation may be important in transformation by simian virus 40.
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PMID:Simian virus 40 large T antigen stably complexes with a 185-kilodalton host protein. 131 Jul 76

DNA samples from 36 hepatocellular carcinoma (HCC) patients from China were screened for a specific mutation affecting codon 249 of the p53 gene, recently identified as a hotspot mutation in some HCCs. We detected the tumor-specific p53 codon 249 mutation in 21 (58%) of 36 HCCs examined. Thirteen patients with the specific codon 249 mutation had lost the remaining allele of p53, whereas the remaining eight patients appeared to have retained both copies of the gene. These results suggest that alterations of p53 may be important events in the genesis of HCCs and that point mutation may precede allele loss.
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PMID:p53 mutations cluster at codon 249 in hepatitis B virus-positive hepatocellular carcinomas from China. 131 38

We analysed the p53 open reading frame (ORF) in 16 small-cell lung cancer (SCLC) cell lines by direct sequencing of cDNA/PCR products and in 20 SCLC tumors by chemical cleavage and single-strand conformation polymorphism analyses of genomic DNA/PCR products. Abnormalities of p53 were found in 16/16 cell lines (100%) and in 16/20 tumors (80%). In the SCLC cell lines, mutations (59% missense, 18% nonsense and 23% splicing) changing the coding sequence were dispersed between amino acids 68 and 342. In the tumor samples, while the mutations occurred predominantly in exons 5-8, other mutations were located outside these regions. G to T transversions were common, occurring in 32% of the cases. We found no p53 mutations in the corresponding normal tissue from 19 patients whose tumors had p53 lesions, indicating that the mutations were all somatically acquired. In analysing the clinical data of the patients we found no correlation between tumor response to therapy or survival and the location or type of mutations. We conclude from these data that: (1) p53 mutations are found in SCLC with high frequency; (2) p53 mutations in a significant fraction of cases generate cDNAs with nonsense or splicing mutations; and (3) to date, these mutations have all been somatically acquired events.
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PMID:High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. 131 96

Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in the mutational hot spots (exons 4-8) of p53 in DNA samples from 40 lung cancers. Most (31 of 40) samples were preselected for LOH in the region of p53. We detected 23 p53 mutations within these exons in 22 lung cancers; no p53 mutations were found in normal tissue of the patients. One-half of the mutations were G to T transversions on the nontranscribed strand, consistent with mutagenesis by tobacco smoke. Mutations of C to A on the nontranscribed strand, which would result from G to T mutations on the transcribed strand, were detected only in one sample. Three of 23 mutations were nonsense mutations; to date, nonsense mutations of p53 have not been reported in lung cancer. Mutation of this p53-coding region was detected in 20 of 27 small cell lung cancer samples, representing a 70% occurrence. Mutation of the p53 gene is apparently very frequent in small cell lung cancers. When LOH in the p53 region could be determined, complete concordance occurred between a sample having both a p53 mutation and LOH in the region of p53 (18 of 18 samples). Twelve samples of lung cancer had LOH in the region of p53, but the samples had no detectable p53 mutations, suggesting either alterations outside the known mutational hot spots of p53 or alterations of another unidentified tumor suppressor gene in the region of p53.
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PMID:p53 mutations in human lung tumors. 131 96

The development of Wilms' tumor, a pediatric kidney cancer, has been linked to the inactivation of a tumor suppressor gene both by epidemiologic studies and by genetic analyses. Like retinoblastoma, Wilms' tumors can occur bilaterally in individuals with apparent genetic susceptibility to this disease. This led Knudson and Strong to propose in 1972 that two genetic events were rate limiting in tumor development and that predisposed individuals had already inherited one mutation in the germline. The observation of karyotype abnormalities in predisposed children and studies of the molecular genetics of Wilms' tumor specimens enabled the identification of chromosome band 11p13 as one genetic locus inactivated in Wilms' tumor. The recent isolation of the WT1 gene, which is the specific target within that locus, offers new insight into the etiology of Wilms' tumor. This gene has properties distinct from those of other known tumor suppressor genes. WT1 encodes a zinc finger transcription factor that is alternatively spliced and has high sequence homology to the early growth response genes (EGR). Unlike the retinoblastoma (RB1) and p53 genes that are expressed ubiquitously, WT1 is expressed in specific cells of the kidney and only during a short period in development. Thus, disruption of a gene that is active during a critical period in the development of a specific organ can lead to neoplastic growth in that organ. Future studies are aimed at exploring the link between the role of the WT1 gene in normal development and in tumorigenesis of the kidney.
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PMID:WT1: a novel tumor suppressor gene inactivated in Wilms' tumor. 131 85


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