Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of C-Ki-ras oncogene by point mutation within codon 12,13 was determined by Polymerase Chain Reaction (PCR) using specific oligonucleotide probes. In 9 of 42 colon cancer specimens point mutations in codon 12 of C-Ki-ras oncogene were found. The point mutations identified were GGT(Gly)----GAT(Asp) (4 cases), GGT (Gly)----TGT (Cys) (3 cases) and GGT(Gly)----GTT(Val) (2 cases), respectively. Two types of point mutations (GGT----GAT, GGT----TGT) were found simultaneously in one specimen. The results showed that there was no relationship between the point mutation of C-Ki-ras oncogene and patient's sex, age, state of metastasis or prognosis.
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PMID:[Detection of point mutations of C-Ki-ras oncogene in colon cancer by PCR using specific oligonucleotide probes]. 139 73

Activation of c-Ki-ras by point mutation within exon 1 was studied in 33 specimens of dysplastic gastrointestinal lesions or of cancers presumed to arise from dysplasia. Samples were obtained from patients with underlying ulcerative colitis or Barrett's esophagus, two diseases associated with dysplasia and increased rates of colonic or esophageal adenocarcinoma, respectively. Genomic DNA was amplified using primers bounding this exon in the polymerase chain reaction. Polymerase chain reaction products were analyzed by direct dideoxy sequencing. Three point mutations in codon 13 of c-Ki-ras were found, all in colonic specimens (two high-grade dysplasias and one adenocarcinoma arising in ulcerative colitis). No point mutations were observed in the second exon of c-Ki-ras or in and around codons 12, 13, and 61 of c-N-ras and C-Ha-ras in a partial sampling of the specimens. These data indicate that ras family protooncogene activation is an uncommon event at this level of malignant progression in these disease states. Carcinogenesis in ulcerative colitis and Barrett's esophagus may proceed via different pathways than in sporadic colon cancer, perhaps involving loss or inactivation of suppressor genes.
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PMID:Activation of c-Ki-ras in human gastrointestinal dysplasias determined by direct sequencing of polymerase chain reaction products. 218 99

c-Ki-ras mutations were analyzed from quintuple colon tumors in a 75-year-old patient with no family history of colon cancer. Polymerase chain reaction-amplified DNA was sequenced for mutations in c-Ki-ras exon 1. Detected mutations were confirmed with allele-specific PCR which amplified only mutant sequences. Five tumors were histopathologically diagnosed as: adenoma with moderate atypia, adenoma with moderate atypia bearing a focal cancer, adenoma with severe atypia bearing a focal cancer, intramucosal carcinoma, well differentiated adenocarcinoma (advanced). Transitions, G-A, were found at the second base of codon 12 for the adenoma with severe atypia bearing a focal cancer and for the well- differentiated adenocarcinoma. The same substitution was found at the second base of codon 13 in the adenoma with mild atypia bearing a focal cancer. No base substitution at codon 12 or 13 was found for the intramucosal carcinoma nor for the adenoma with moderate atypia. These findings demonstrated there to be heterogeneous genetic and histopathological alterations in the individual tumors of the present case of synchronous malignancy of the colon.
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PMID:Mutational heterogeneity among individual tumors in a case of multiple primary malignancy of the colon. 828 88

We report a protocol which can analyze DNA by the dideoxy method. First, we prepared DNA from paraffin specimen of colon cancer and normal tissue by the method using proteinase and phenol. Polymerase chain reaction (PCR) was performed as follows. The primers used were oligonucleotides corresponding to the sequence of exon 5 on p53. An initial denaturing step was carried out at 94 degrees C for 2 min. Products were amplified for 40 cycles at 94 degrees C for 1 min, 60 degrees C for 1 min, and 72 degrees C for 1 min. Specific PCR products derived from p53 gene were purified. Protocol for the PCR-sequencing reaction: The reaction mixture was divided into four 4 microliters fraction. Each fraction was mixed with 2 microliters of NTP solution including non-RI dideoxynucleotides (TOYOBO). PCR was carried out as follows: an initial denaturing step at 94 degrees C for 1 min, then 30 cycles at 94 degrees C for 1 min, 60 degrees C for 1 min, and 72 degrees C for 1 min. Prior to loading in a denaturing 8% polyacrylamide-6M Urea gel, the samples were heated to 94 degrees C for 2 min then quickly chilled in ice-water. Electrophoresis was carried out at 1000V for 3hr and transcribed to a nylon membrane. The ladders of DNA were obtained by Non-RI Detection Kit (TOYOBO). We determined the sequence of 167 nucleotides. Results indicated that the point mutations in DNA could be easily detected.
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PMID:[Detection of nucleotide mutation by direct sequencing method using non-radio isotopic marker]. 925 14

The cyclin D1/CCND1 oncogene (PRAD1) is amplified in 15% of primary human breast cancers and overexpressed in 30-50% of breast cancers, suggesting that mechanisms in addition to DNA amplification may lead to deregulated expression of this gene in breast cancer. Cyclin D1 overexpression at a higher frequency than gene amplification is also seen in a variety of other tumors. Cyclin D1 overexpression without amplification could result from a trans-acting regulatory disturbance or could be a consequence of a clonal regulatory mutation in one allele of the gene. We have, therefore, examined whether the overexpression of cyclin D1 mRNA is derived from one parental allele or both alleles in tumor cell lines with or without amplification of the cyclin D1 gene. Eight tumor cell lines, MCF-7, SK-BR-3, ZR-75-1, U-2-OS, SK-LMS-1, DLD1, HCT15, and HT29, out of 20 tumor cells initially examined were found to be heterozygous at the polymorphic NciI site within exon 4 of the cyclin D1 gene. Polymerase chain reaction and NciI digestion (PCR-RFLP) analysis of genomic DNA demonstrated DNA amplification of one allele in the ZR-75-1 cells and HT29 cells and no such imbalance in cyclin D1 gene copy number in the other cells, consistent with Southern blot analyses. Reverse-transcription polymerase chain reaction analysis and NciI digestion (RT-PCR-RFLP) of total cDNA revealed that the overexpressed cyclin D1 mRNA is preferentially derived from the amplified allele in the ZR-75-1 and HT29 cells. In contrast, the other tumor cells overexpressed cyclin D1 mRNA equally from both alleles. This finding strongly suggests that, in breast, sarcoma, and in colon cancer cells with cyclin D1 overexpression and normal gene copy number, elevated levels of cyclin D1 mRNA result from a trans-acting influence on both alleles rather than a clonal somatic mutation or rearrangement in or near a single cyclin D1 gene.
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PMID:Mechanism of cyclin D1 (CCND1, PRAD1) overexpression in human cancer cells: analysis of allele-specific expression. 959 36

Expression of Fas, an apoptosis-inducing receptor, in colonic epithelium is progressively reduced during malignant transformation. We have examined the human Fas gene for loss of heterozygosity (LOH) and gross rearrangements in colon tumours and matched normal mucosa. Polymerase chain reaction (PCR) primers were designed to span a DraI restriction fragment length polymorphic site in the gene. Heterozygosity was detected in normal DNA samples by PCR amplification of the polymorphic site and restriction enzyme digestion. Thirty-eight of 88 patients (43%) with colon carcinomas were informative for the assay, and LOH was detected in 6 of the 38 (16%) corresponding tumours. Tumours from three patients with LOH did not express detectable Fas mRNA, and Fas expression was reduced or absent in 7 of 11 tumours from informative patients without LOH. Southern blotting of tumour DNA samples was used to detect rearrangement of the Fas gene, but no altered hybridization patterns were observed in 64 tumours analysed. These findings indicate that disruption of the Fas gene is not primarily responsible for the loss of Fas protein expression reported in colon cancer. We have also shown that loss of Fas gene transcription is common in these tumours, which may be due to epigenetic gene silencing.
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PMID:Down-regulation of Fas gene expression in colon cancer is not a result of allelic loss or gene rearrangement. 965 61

A 17-year-old Turkish boy with Bloom syndrome (BS) developed mucinous carcinoma of the transverse colon. He was followed from 2 to 17 years of age. Increased sister chromatid exchanges (SCE) were observed, and he was diagnosed with BS at the age of 7. Sun-sensitive skin lesions were examined by skin biopsy, and histopathological studies of these lesions were done. During the follow-up period, an intraabdominal mass at the transverse colon was found, and mucinous carcinoma of colon was diagnosed at the age of 16. We examined TP53 protein expression from paraffin-embedded colon tissue of the patient with an immunohistochemical method. Polymerase chain reaction products of exons 4-9 of the TP53 gene were examined by SSCP. No evidence of overexpression of TP53 protein or mutations of the TP53 gene was observed. The patient in this report is the first case with a mucinous carcinoma of colon diagnosed at an early age in the Bloom Syndrome Registry. Based on our results, carcinoma of the colon in BS patient may occur earlier than 35 years of age and the TP53 gene may not be directly related to carcinoma in Bloom syndrome.
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PMID:Mucinous carcinoma of the colon in a 16-year-old Turkish boy with Bloom syndrome: cytogenetic, histopathologic, TP53 gene and protein expression studies. 1032 90

We determined the prognostic role of K-ras mutation in tumor tissue of patients with refractory colon cancer who received Marimastat (BB2516). DNA was extracted from paraffin-stored tumor tissue of 27 patients who previously failed 5-fluorouracil and were treated with BB2516. The presence of K-ras mutation was characterized by Polymerase Chain Reaction using ras- and p53-specific primers. ras and p53 oncoprotein expression was analyzed by an automated biotin-avidin immunoproxidase technique. Seventeen patients had a normal K-ras sequence and 10 patients had a K-ras mutation. Median survival of patients with a normal ras sequence was 330 days from the time of BB2516 treatment compared with 160 days for patients with a K-ras mutation (p = 0.0442, Wilcoxon; 0.0130 Log-Rank). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed. Abnormalities involving ras expression did not affect survival. By comparison, median survival for patients with p53 mutation or p53 overexpression was both 158 days after BB2516 treatment. Patients having both K-ras and p53 mutations had the poorest median survival of 113 days (p = 0.035). There is a suggestion by univariate analysis that the presence of a K-ras mutation may predict survival in patients with progressive colon cancer. Further assessment with larger patient numbers and multivariate analysis is indicated.
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PMID:Prognostic role of K-ras in patients with progressive colon cancer who received treatment with Marimastat (BB2516). 1075 86

We have found a significant concordance between the in vitro replication errors of human DNA polymerase beta and in vivo point mutations of the adenomatous polyposis coli (APC) gene that leads to colon cancer. We determined the error spectrum of DNA polymerase beta in the human APC gene under PCR conditions and compared it with the set of mutations reported in human colon tumors. Polymerase beta created seven hotspot mutations within 141 target bp analyzed in APC exon 15. Three of these polymerase beta hotspots, 2 frameshifts and a bp substitution mutation, were concordant with 3 of 13 APC hotspots detected in human colon cancers in the same DNA sequences. These 3 concordant hotspots accounted for some 54% of reported in vivo APC hotspot mutations. Using the assumption of a hypergeometric distribution of hotspot mutations among bp of the scanned sequences, the probability of this concordance occurring by chance is <4 x 10(-4). These data support the hypothesis that DNA polymerase beta errors are an important fraction of cancer-causing APC mutations.
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PMID:The DNA polymerase beta replication error spectrum in the adenomatous polyposis coli gene contains human colon tumor mutational hotspots. 1203 44

In a previous study, a data mining tool called Digital Differential Display (DDD) from the Cancer Genome Anatomy Project (CGAP) was used to predict solid tumor- and organ-specific genes from the expressed sequence tag (EST) database. To validate the use of bioinformatics approaches in gene discovery, one of the ESTs, which was predicted to be colon tumor-specific, was chosen for further study. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis of matched sets of cDNAs from normal and colon tumor tissues indicated that the EST was specifically expressed in the majority of colon tumors. Expression was also detected in early adenomas. Among other normal tissues, EST expression was detected only in the small intestine. The colon tumor specificity of this EST was inferred from the lack of expression in carcinomas of the breast, lung, ovary, pancreas and prostate. To validate the computational prediction of specificity, a full-length cDNA encompassing the entire open reading frame was cloned and, in view of its apparent specificity to the colon tumors, this gene was termed Colon Carcinoma Related Gene (CCRG). CCRG encodes a novel cysteine-rich motif and a putative signal peptide sequence. Supernatant from COS cells transfected with the CCRG expression vector stimulated proliferation of colon cancer cells. Immunoreactive CCRG was also detected in the paraffin sections of colon tumor samples. CCRG belongs to a new class of growth factors and may be important in the diagnosis and treatment of colon cancers. Identification of CCRG using bioinformatics approaches validates gene discovery using computational approaches.
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PMID:Bioinformatics-based discovery of a novel factor with apparent specificity to colon cancer. 1222 33


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