Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies

Hafner, Christian; Knuechel, Ruth; Stoehr, Robert; Hartmann, Arndt

doi:10.1002/ijc.10544

Cited by 174 publications

(113 citation statements)

References 71 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…In addition, there might be more than one molecular pathway contributing to the development of recurrent tumors. Nevertheless, a high significance for the GO-category cell adhesion observed among the 49 genes, as well as in the gene predictor described by Dyrskjt and co-workers, suggests that the identified genes may be compatible with processes involved in tumor recurrences (Hafner et al, 2002).…”

Section: Expression Profiling Of Urothelial Carcinoma D Lindgren Et Almentioning

confidence: 82%

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

et al. 2006

View full text Add to dashboard Cite

We used gene expression profiling, mutation analyses of FGFR3 and TP53, and LOH analyses of chromosome 9 and the TP53 region on chromosome arm 17p, to molecularly characterize 75 Ta and T1 bladder carcinomas. We identified four major cellular processes related to cell cycle, protein synthesis, immune response, and extra cellular components that contribute to the expressional heterogeneity of early-stage urothelial cell carcinoma (UCC). Activating FGFR3 mutations were found at the highest frequency in G1 tumors (80%), and showed a strong correlation with FGFR3 expression. In contrast, G3 tumors displayed mutations in less than 10% of the cases and a low level of FGFR3 expression. Even though LOH on chromosome 9 was not associated with any specific expression pattern, our data indicate that loss of chromosome 9 is associated with tumor development rather than initiation. The combined analyses suggest the existence of two types of UCC tumors, one which is characterized by FGFR3 mutation or expression, high expression of protein synthesis genes, and low expression of cell cycle genes. Furthermore, the presented data underscore FGFR3 receptor involvement in urothelial cell transformation as the presence of FGFR3 mutations has a major impact on the global gene expression profile of bladder carcinomas.

show abstract

Section: Expression Profiling Of Urothelial Carcinoma D Lindgren Et Almentioning

confidence: 82%

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Multifocality then arises secondary to either intraluminal shedding of tumor cells with secondary implantation at different urothelial sites or secondary to intraepithelial migration (45). The possible role of intraluminal spread of tumor cells in tumor multifocality is supported by the finding that later recurrences often occur downstream from the site of the original tumor.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been suggested that oligoclonality is more common in early lesions with progression to higher stages leading to the overgrowth of one clone and pseudomonoclonality (20,45). Thus, early or preneoplastic lesions may arise independently with a specific clone undergoing malignant transformation, which subsequently spreads through the urothelium by either an intraluminal or intraepithelial mechanism producing multifocal tumors of monoclonal origin.…”

Section: Discussionmentioning

confidence: 99%

Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis

Jones¹,

Wang²,

Eble³

et al. 2005

Clinical Cancer Research

170

View full text Add to dashboard Cite

Purpose: Human urothelial carcinoma is thought to arise from a field change that affects the entire urothelium. Multifocality of urothelial carcinoma is a common finding at endoscopy and surgery. Whether these coexisting tumors arise independently or are derived from the same tumor clone is uncertain. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in the cells from each coexisting tumor may further our understanding of urothelial carcinogenesis. Experimental Design: We examined 58 tumors from 21patients who underwent surgical excision for urothelial carcinoma. All patients had multiple separate foci of urothelial carcinoma (two to four) within the urinary tract. Genomic DNA samples were prepared from formalin-fixed, paraffinembedded tissue sections using laser-capture microdissection. Loss of heterozygosity (LOH) assays for three microsatellite polymorphic markers on chromosome 9p21 (IFNA and D9S171), regions of putative tumor suppressor gene p16, and on chromosome17p13 (TP53), the p53 tumor suppressor gene locus, were done. X-chromosome inactivation analysis was done on the urothelial tumors from 11female patients. Results: Seventeen of 21 (81%) cases showed allelic loss in one or more of the urothelial tumors in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between each coexisting urothelial tumor were seen in only 3 of 21 (14%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting urothelial tumors was seen in only 3 of 11 female patients; of these 3 cases, only one displayed an identical allelic loss pattern in all of the tumors on LOH analysis. Conclusion: LOH and X-chromosome inactivation assays show that the coexisting tumors in many cases of multifocal urothelial carcinoma have a unique clonal origin and arise from independently transformed progenitor urothelial cells, supporting the ''field effect'' theory for urothelial carcinogenesis.

show abstract

“…a unique gene expression profile already existing in the non-malignant thyroid tissue that differentiates the hyperplastic thyroid epithelial cells of MG with unsuspected PTC from MG without PTC [10][11][12]. Our global gene expression analysis of these two groups of goiters (MNG and HN + PTC) suggested that indeed environmental or genetic factors exist that might alter the overall gene expression profile in the thyroid epithelial cells making them susceptible to further transformation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Background May Confer Susceptibility to PTC in Benign Multinodular Thyroid Disease

Thavarajah¹,

Weber²

2012

JCT

View full text Add to dashboard Cite

Purpose: The incidence of hyperplastic thyroid nodular disease has been consistently rising over the last decades. In addition, unsuspected papillary thyroid carcinoma (PTC) can be found in up to 34% of patients operated for benign thyroid lesions. PTC tends to occur multi-focally and is commonly of polyclonal origin. We set out to test the hypothesis that in benign thyroid disease, a unique genetic signature can already be identified in the benign pathology, which is associated with a susceptibility of the thyroid tissue to neoplastic transformation in the context of additional growth promoting stimuli. Patients and Methods: We obtained a set of 23 samples from patients with multinodular goiter (MNG), 12 of whom also harbored an unsuspected PTC. We used global gene expression analysis to evaluate for dissimilarities in the gene expression patterns between these two groups. We also compared these patterns to the profiles of 3 normal thyroid and 7 PTC samples. Results: We were able to accurately distinguish between hyperplastic nodules of patients with multinodular goiter and those that were associated with a PTC. One of the strongest differentially expressed genes, CDC42, has been implicated to respond to environmental factors such as UVB radiation and might point to novel factors contributing to PTC genesis in the setting of pre-existing benign proliferative disease. Conclusion: While the comparison between histologically identical samples cannot distinguish the two groups of goiters, unsupervised or supervised approaches allowed us to identify a molecular signature associated with PTC susceptibility in multinodular goiter.

show abstract

Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies

Cited by 174 publications

References 71 publications

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis

Genetic Background May Confer Susceptibility to PTC in Benign Multinodular Thyroid Disease

Contact Info

Product

Resources

About