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Sporadic Basal Cell Carcinoma (sporadic + basal_cell_carcinoma)
Selected AbstractsInsight into the pathogenesis of sporadic basal cell carcinomaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2004Zuzana Holíková Sporadic basal cell carcinoma (BCC) is the commonest human cancer. Although its aggressiveness is low and metastatic potential negligible, the increasing incidence of the tumor in the Western world drives attention to its pathogenesis. In 1996, germ-line mutations in the patched receptor of the Sonic hedgehog (Shh) signaling pathway were described in the Gorlin,Goltz syndrome in association with multiple nevoid BCCs. Later, the aberrant activation of the Shh was identified in sporadic BCCs as well. Recently, the role of other tumor suppressors and DNA repair gene mutations and their relationship with UV radiation-induced DNA damage have been elucidated. [source] Genetics of basal cell carcinomaAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 2 2010Sally E De Zwaan ABSTRACT Basal cell carcinoma is the most common human malignancy in populations of European origin, and Australia has the highest incidence of basal cell carcinoma in the world. Great advances in the understanding of the genetics of this cancer have occurred in recent years. Mutations of the patched 1 gene (PTCH1) lead to basal cell carcinoma predisposition in Gorlin syndrome. PTCH1 is part of the hedgehog signalling pathway, and derangements within this pathway are now known to be important in the carcinogenesis of many different cancers including sporadic basal cell carcinoma. The molecular biology of the hedgehog pathway is discussed, and mouse models of basal cell carcinoma based on this pathway are explored. New developments in non-surgical treatment of basal cell carcinoma are based on this knowledge. Other genes of importance to basal cell carcinoma development include the tumour suppressor gene P53 and the melanocortin-1 receptor gene. In addition, we discuss molecules of possible importance such as the glutathione-S-transferases, DNA repair genes, cyclin-dependent kinase inhibitor 2A, Brahma and connexins. Evidence of familial aggregation of this cancer is explored and supports the possibility of genetic predisposition to this common malignancy. [source] Immunohistochemical detection for nuclear ,-catenin in sporadic basal cell carcinomaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2001F. Yamazaki Background Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt-mediated signalling pathway may be one of the downstream targets of sonic hedgehog -mediated signalling, which has led us to focus on molecular events on the Wnt pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that ,-catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, ,-catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes. Objectives To investigate the cellular distribution of ,-catenin in skin tumours, in particular, in BCC. Methods Twenty skin biopsy specimens derived from BCC, 10 from inflammatory skin diseases and five from squamous cell carcinomas were immunostained with an antibody directed against ,-catenin. Results Fourteen of the 20 BCC samples tested showed nuclear localization of ,-catenin, while none of the other samples gave rise to positive nuclear staining. Conclusions Nuclear localization of ,-catenin is a characteristic feature of BCC; this suggests its tumorigenic role in this tumour. This gives us a further insight into the molecular pathogenesis of BCC. [source] Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant-negative mechanismDEVELOPMENTAL DYNAMICS, Issue 4 2004Gary R. Hime Abstract Mutations in the human homolog of the patched gene are associated with the developmental (and cancer predisposition) condition Nevoid Basal Cell Carcinoma Syndrome (NBCCS), as well as with sporadic basal cell carcinomas. Most mutations that have been identified in the germline of NBCCS patients are truncating or frameshift mutations, with amino acid substitutions rarely found. We show that a missense mutation in the sterol-sensing domain G509V acts as a dominant negative when assayed in vivo in Drosophila. Ectopic expression of a Drosophila patched transgene, carrying the analogous mutation to G509V, causes ectopic activation of Hedgehog target genes and ectopic membrane stabilisation of Smoothened. The G509V transgene behaves in a manner similar, except in its subcellular distribution, to a C-terminal truncation that has been characterised previously as a dominant-negative protein. G509V exhibits vesicular localisation identical to the wild-type protein, but the C-terminal truncated Patched molecule is localised predominantly to the plasma membrane. This finding suggests that dominant-negative function can be conferred by interruption of different aspects of Patched protein behaviour. Another mutation at the same residue, G509R, did not exhibit dominant-negative activity, suggesting that simple removal of the glycine at 509 is not sufficient to impart dominant-negative function. Developmental Dynamics 229:780,790, 2004. © 2004 Wiley-Liss, Inc. [source] | ||||||||||