Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urothelial carcinoma of the renal pelvis and ureter may develop sporadically or as a manifestation of hereditary nonpolyposis colorectal cancer. The majority of hereditary nonpolyposis colorectal cancer is caused by mutation of the human DNA mismatch repair (MMR) genes and is detected by associated microsatellite instability (MSI). Seventy-three unselected urothelial carcinomas of the ureter and/or renal pelvis were screened for MSI using the National Cancer Institute-designated reference panel (plus BAT40). Instability of at least two microsatellite markers (MSI-high) was detected in 15 samples (21%). Immunohistochemical staining of the MMR proteins (hMSH2, hMLH1, or hMSH6) was absent in 13 of 15 (87%) MSI tumors, and alteration of coding sequence microsatellites (TGFbetaRII, Bax, hMSH3, and hMSH6) was found at frequencies of 7-33% in these samples. Tumors with MSI had significantly different clinical and histopathological features including higher prevalence in female patients, low tumor stage and grade, and a papillary and frequently inverted growth pattern. Our results suggest a molecular pathway of tumorigenesis that is similar to MMR-deficient colorectal cancers and consistent with the notion that the site distributions of hereditary or sporadic MSI-high tumors may reflect tissue-specific susceptibility to lesions processed by the MMR machinery.
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PMID:Frequent microsatellite instability in sporadic tumors of the upper urinary tract. 1246 Aug 87

The multistep development of malignant tumors with increasing accumulation of genetic alterations from preneoplastic lesions to invasive carcinoma is an accepted model of carcinogenesis. Urothelial carcinoma of the bladder and upper urinary tract is an interesting model system to study tumor development and progression. There is both clinical and molecular evidence that urothelial carcinoma can be divided in two groups with different characteristics: 1) well differentiated genetic stable and mostly superficial papillary tumors with frequent recurrence and low progression risk and 2) poorly differentiated mostly solid and invasive tumors with a high number of genetic alterations. The aim of the studies summarized in this manuscript were: 1) to identify genetic changes with importance for urothelial carcinogenesis by investigation of preneoplastic and early neoplastic urothelial lesions, 2) to define molecular markers for progression of papillary carcinoma, and 3) to investigate the importance of microsatellite instability and mismatch repair defects for development of tumors of the upper urinary tract which are frequently found within the HNPCC syndrome. The investigation of urothelial hyperplasias, dysplasias and carcinoma in situ by deletion mapping (LOH analysis), FISH, CGH and mutation detection revealed that urothelial hyperplasias are precursors of papillary bladder tumors and flat dysplasias can be regarded as precursors of solid bladder cancers. In bladder cancer patients, there are genetic alterations already detectable in histologically inconspicous urothelium. The investigation of papillary bladder cancers for progression-related genetic alterations showed that mutations in the wnt pathway genes APC and beta-Catenin do not play an important role in urothelial carcinogenesis. Instead, the expression of the antagonistic wnt-related genes WIF-1 and sFRPI is strongly reduced in bladder cancer and associated with poor prognosis in papillary tumors. Loss of sFRP1 expression is not due to gene mutation but to epigenetic inactivation by promoter hypermethylation and is related to deletions at chromosome 8p12. In contrast to bladder cancers, tumors of the ureter and renal pelvis develop through a different genetic pathway in 30% of cases. The loss of mismatch repair proteins (hMSH2, hMLH1 or hMSH6) leads to a mutator phenotype with accumulation of genetic alterations in multiple repetitive sequences (microsatellite instability, MSI). MSI-positive tumors were predominantly located in the ureter and showed a lower tumor stage and grade and papillary and frequently inverted growth pattern. They were more frequent in females and younger patients and had a higher incidence of colorectal carcinomas and other tumors in the family. Chromosome 9 deletions, a hallmark of urothelial carcinomas, and the number of chromosomal alterations as detected by CGH analysis were significantly less frequent in these tumors. These data strongly suggest a distinct molecular pathway in the development of upper urinary tract tumors with mutator phenotype.
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PMID:[Molecular changes in development and progression of urothelial carcinoma]. 1688 10

Lynch Syndrome (LS) is a cancer susceptibility syndrome caused mostly by mutations in the mismatch repair genes, hMLH1, hMSH2 and hMSH6. Mutation carriers are at risk of colorectal and endometrial cancer and, less frequently, cancer of the ovaries, stomach, small bowel, hepatobiliary tract, ureter, renal pelvis and brain. The influence of environmental factors on extracolonic cancer risk in LS patients has not been investigated thus far. The aim of this study was to investigate some of these factors in South African females carrying the hMLH1 c.C1528T mutation and their mutation-negative relatives. Data were collected from 87 mutation-positive females and 121 mutation-negative female relatives regarding age, cancer history, hormonal contraceptive use, parity, duration of breast feeding, height, weight and age at first birth, last birth, menarche and menopause. Influence of these factors on cancer risk was analysed by mixed-effects generalised linear models. Extracolonic cancer occurred in 14% (12/87) of mutation-positive females versus 7% (8/121) of mutation-negative females, (P = 0.0279, adjusted for age and relatedness between women). Breast cancer was the most common extracolonic cancer. An association was found for oral contraceptive use and extracolonic cancer risk in mutation-negative females only. No association was found for any of the other risk factors investigated, when adjusted for age. This might be due to the scarcity of extracolonic cancers in our data. Future knowledge on the influence of additional environmental factors on cancer risk in LS females can lead to evidence-based lifestyle advice for mutation carriers, thereby complementing the prevention strategies available today. In addition, it can contribute to an integrated model of cancer aetiology. Therefore, this study should be taken as a thrust for further research.
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PMID:Lynch syndrome: the influence of environmental factors on extracolonic cancer risk in hMLH1 c.C1528T mutation carriers and their mutation-negative sisters. 2064 May 20