Work

Identification of novel tumour suppressor genes involved in the development of cutaneous malignant melanoma

Year: 2009
Type: dissertation
Abstract: Skin cancer is one of the most common forms of adult solid tumour. The incidence is \nincreasing rapidly making skin cancer a major health problem in several countries. \nCutaneous Malignant Melanoma (CMM) is the least common but the most life \nthreatening type of skin cancers and is responsible for 90% of all skin malignancy \nassociated deaths. \nThe precise cellular and molecular etiology of malignant melanoma is quite complex \nand the molecular events directly related to melanoma progression are yet to be \nelucidated. However, recent advances in molecular biology have resulted in a clearer \nunderstanding of the cellular and molecular events of skin cancer development. The \nbest-characterized locus associated with CMM development is the CDKN2A that maps \nto chromosome 9p21 and encodes for the cell cycle regulator p16 tumour suppressor \ngene (TSG), and is frequently inactivated in melanoma tumours. In addition to p16, \nother loci located in 9p21 appear to be important in CMM development and functional \nevidence for the presence of TSG(s) has been provided (Parris et al., 1999). The aim of \nour study is to contribute to the understanding of CMM development by isolating and \ncharacterising novel TSG(s) at this location. \nIn order to pursue identifying potential TSG(s), we have developed several \nmonochromosome hybrids using microcell mediated chromosome transfer, and \nevaluated the tumourigenicity of the constructed hybrids by anchorage independent \ngrowth in soft agar. For the molecular biology aspects, expression analysis of the genes \nin the 9p21 region was carried out by reverse transcription PCR. Potential candidate \ntumour suppressor genes were then carefully evaluated by generating expression \nprofiles via conducting real time PCR. Experimental evidence is provided which \nsupports the candidacy of interferon alpha 1 (IFNA1) as a tumour suppressor gene for \nmelanoma development.
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: green
OpenAlex ID: W2127125144
Cites: 189
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Related to: 10