Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DCC (deleted in colorectal cancer) gene was originally identified as a candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may also be reduced in colon cancers. We have used monoclonal antibodies generated against the DCC immunoglobulin-like domain to investigate DCC isoforms and DCC protein expression during colon cancer progression. Normal mucosa and colonic tumour specimens representative of the range of colonic tumour progression from benign adenomatous polyps to metastases were compared by Western blot analyses. We show that while M(r) 194 000 DCC is present in normal colonic mucosa and adenomatous polyps, it is also similarly expressed in colorectal carcinomas and colonic metastases in the liver. The presence of DCC protein is consistent with the presence of DCC mRNA transcripts in the same tissue specimens. Notably DCC was not completely lost in any colonic tumour specimens examined, even those that had progressed to metastatic cancers. Quantitation of DCC protein expression in tissue specimens by densitometry demonstrated that both normal and malignant specimens exhibit a wide range of DCC protein levels and there was no significant correlation between diminished DCC protein expression and colon cancer progression. These results demonstrate the pattern of expression of the DCC gene product in colonic tumour progression and show that absence of DCC expression is not associated with colonic tumour progression.
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PMID:The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases. 876

Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer. The aim of this study was to further characterize these regions. We investigated 20 polymorphic regions on the 3 chromosome arms in 43 cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH on 22q implies that this locus has no significant role in prostate carcinogenesis. At DCC, although the overall incidence was low, tumours with LOH were mostly of high grade or had metastases, suggesting a role for this gene in prostate cancer progression. On chromosome 8p, 29% of cancers had deletions at the LPL locus on 8p22 and 60% had deletions within a region flanked by the markers D8S339 and ANKI on 8p 11.1-p21.1. Within this region, 2 distinct areas of allelic loss were observed, at one or both ANKI and D8S255, and in the region defined by the markers D8S259-D8S505. For the regions 8p22 and ANKI-D8S255, tumours with metastases had a greater frequency of LOH compared to non-metastasizing tumours, suggesting the presence of putative metastasis-suppressor genes in these regions.
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PMID:Allelic loss on chromosomes 8p, 22q and 18q (DCC) in human prostate cancer. 879 71

A characteristic feature of colorectal cancer genesis is its stepwise progression, which offers unique possibilities for studying its development. There are two principal kinds of mutation leading to uncontrolled cell proliferation and cancer. The first renders a stimulatory gene hyperactive--generation of an oncogene--and the second is the inactivation of a tumour suppressor gene. Current knowledge suggest that the change from normal mucosa to a small adenoma may be mediated by mutations of the APC gene and MCC gene on chromosome 5, by chromosome 5 deletion, by c-myc activation, and by DNA hypomethylation. The development to a large adenoma may be caused by Ki-ras mutation and further change to a dysplastic adenoma by deletion of the DCC gene on chromosome 18. The ability to become an invasive carcinoma may then be mediated by p53 mutations and deletion of chromosome 17p. Identification of genetic markers for metastatic disease is under progress.
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PMID:Genetic aspects of colorectal cancer: the surgeon's view. 889 51

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

Inactivation of the DCC (Deleted in Colon Carcinoma) tumor suppressor gene by allelic loss and/or reduced expression is associated with the development of colon cancer, gliomas, gastric and prostatic malignancies. In a total cohort of 51 testicular germ cell tumors (GCT) of different histologies we analyzed restriction fragment length polymorphism (RFLP) for DCC at two specific DNA sites in 37 GCT and DCC mRNA expression compared to that of the adjacent normal testicular tissue in 41 GCT, one Leydig cell tumor and one testicular metastasis of a non-small cell lung cancer (NSCLC). Two of 17 tumors (11.7%) informative for the Msp I polymorphic site of the DCC gene and 6/25 tumors (24.0%) informative for variable number of tandem repeat (VNTR) showed loss of heterozygosity (LOH). DCC expression was analyzed by semi-quantitative polymerase chain reaction after initial reverse transcription (RT-PCR). Thirty of 41 GCT (73.1%) and both, the Leydig cell tumor and the testicular metastasis of NSCLC, had a nearly complete or total loss of DCC mRNA expression. Six of 11 (54.5%) seminomas and 24/30 (80.0%) nonseminomas had this loss of expression. Twelve of 17 (70.5%) localized tumors, 9/13 (69.2%) tumors with lymph node involvement and 9/11 (82.2%) tumors with distant metastases showed decreased or absent DCC expression. This data suggests that inactivation of the DCC gene, especially the loss of DCC expression, is associated with the development and progression of human GCT.
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PMID:Analysis of the DCC tumor suppressor gene in testicular germ cell tumors: mutations and loss of expression. 911 74

Microsatellite instability (MSI) is intrinsic to most colorectal carcinomas (CRC) from patients with hereditary nonpolyposis colorectal cancer (HNPCC), reflecting germline mutations in the mismatch-repair (MMR) genes. Its occurrence and chronological sequence of development in sporadic CRC appears less well defined. To explore the time sequence in acquisition of MSI, and the role it plays during tumor progression in sporadic CRC, we compared the incidence of MSI in tissue samples from 40 Dukes'-B and 30 Dukes'-D CRC patients with liver metastases, at 4 different microsatellite loci, representing sites on the APC, DCC and p53 genes respectively as well as the D2S123 site. Among the 30 patients with hepatic metastases, MSI was found in 9 (30%) of the primary, and 13 (43.3%) of the metastatic tumors. In comparison, among the 40 Dukes'-B CRC, MSI was found in only 8 cases (20%). CRC with MSI were more frequently located in the right colon, less frequently on the left side, and seldom in the rectum. Tumor ploidy analysis shows that 46.2% of Dukes'-D primary tumors with MSI are diploid (chi2 = 4.46, p = 0.035). With a mean follow-up time of 4.2 years for the Dukes'-B CRC, there were no recurrences in the 8 patients with MSI, whilst 6 (18.8%) relapses occurred amongst the 32 patients without MSI, average time to recurrence being 15 months. In Dukes'-D CRC, mean survival time for patients with MSI was 37 months (95% CI, 24 to 51 months), for those without MSI 26 months (95% CI, 18 to 35 months), although this was not statistically significant. Our data suggest that tumor progression may involve increased genetic instability.
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PMID:Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases. 929 42

To evaluate the role of DCC gene alteration in the development and progression of gastric cancer, loss of heterozygosity (LOH) and mRNA expression of DCC gene was examined in surgically resected gastric cancer specimens using PCR-RFLP and RT-PCR analyses. LOH was detected in 18 (35.3%) of 51 informative cancers specimens. The frequency of LOH in stages III and IV (50.0%) was significantly higher than that in stages I and II (14.3%, P < 0.05%), but LOH was not correlated to histological types, tumor size, invasion depth and lymph node metastases. Expression of DCC mRNA in 26/51 cases was examined and the DCC expression was lost in 8/26 (30.7%) cancer, and no significant correlation was found between loss of DCC expression or LOH and clinico-pathologic parameters. LOH and loss of expression at DCC gene occur frequently in gastric cancers, LOH at DCC locus is a late event.
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PMID:[A study of loss of heterozygosity and mRNA expression at DCC locus in gastric cancers]. 938 68

DCC gene located at chromosome 18q21.3 is an important tumor-supressor gene associated with tumorigenesis and progression, especially in colorectal carcinomas. Adopting Southern blot technique and RFLP analysis, 33 primary Chinese colorectal cancer patients were examined for loss of heterozygosity (LOH) of DCC gene. Among 16 informative cases, 6 (38%) showed allelic deletion. 18q LOH was correlated with lymph node and hepatic metastases (P < 0.05). The results indicate that application of molecular genetics is of value in ascertaining the metastatic potential of colorectal carcinomas.
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PMID:[Loss of heterozygosity involving DCC gene in human colorectal cancers is correlated with the metastatic potential]. 938 12

Apoptosis (programmed cell death) inhibition may be an important mechanism by which gastrointestinal mucosal cells containing damaged DNA evade normal clearance mechanisms and grow to become invasive tumours. Since bcl-2 is an apoptosis inhibitor, bcl-2 mRNA expression was measured in 21 metastases of colorectal cancer using reverse transcription-polymerase chain reaction analysis. The mean bcl-2 mRNA expression (0.45 U, P < 0.0001) was lower than that of normal mucosal controls (= 1 U). p53 expression was inversely correlated with bcl-2 expression (P = 0.021) in 19 evaluable samples, and in tumours where p53 expression was over twice that of normal colonic mucosal values, bcl-2 mRNA was significantly decreased (mean 0.30, P = 0.0052). c-myc was also inversely correlated with bcl-2 expression (P = 0.025). Decreased bcl-2 expression in metastatic colorectal cancer may be partly due to allelic loss, given the proximity of bcl-2 to the frequently deleted DCC gene on chromosome 18q. However, the inverse correlation to p53/c-myc suggests an active downregulation of bcl-2, possibly following delegation of its apoptosis inhibiting role to other genes.
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PMID:bcl-2 expression is reciprocal to p53 and c-myc expression in metastatic human colorectal cancer. 984 90

Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies of CIN lesions, primary cervical carcinoma, and metastases may shed light on the relative importance of various genetic alterations involved in the progression of CIN to invasive carcinoma. We examined tumor material from 10 patients with squamous cell carcinoma of the uterine cervix and synchronous CIN lesions and lymph node metastases. The CIN component, invasive carcinoma, and lymph node metastases were analyzed separately for loss of heterozygosity (LOH) on the following loci: VHL (3p21), HLA region (6p22-23), PGL (11q 22-24), E6 associated protein (15q11-13), TP53 (17p13), DCC (18q21.1), and chromosomes 1, 2, 4, 9, 20, and X. Using immunohistochemistry, the expression of the EGF receptor, ERBB2, and TP53 was determined. In CIN lesions, frequent LOH was found at chromosome arms 3p, 6p, and 11q. Primary invasive carcinoma showed additional LOH at chromosome arms 6q, 17p, and 18q. In lymph node metastases, an additional locus on the X chromosome displayed LOH. All carcinomas and synchronous lesions but one showed high expression levels of the EGF receptor. TP53 staining, when present, was found in all synchronous lesions. Focal staining of ERBB2 was found in one CIN lesion, two invasive carcinomas, and four metastases. The molecular alterations accumulated in a fashion that paralleled the progression of the tumors. These results indicate that cervical tumorigenesis occurs in a stepwise fashion, including infection and integration of oncogenic HPV and several specific genetic alterations. Genes Chromosomes Cancer 26:346-354, 1999.
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PMID:Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix. 1053 70


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