Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597332
Title: Novel cytogenetic abnormalities in cervical squamous cell carcinoma
Author: Carter, S. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Abstract:
SCC cell lines were karyotyped to identify recurrent aberrations and those providing a selective advantage in individual cases. Karyotypic heterogeneity provided evidence for ongoing chromosomal instability (CIN) in all cell lines but revealed discordance between the levels of numerical CIN (N-CIN) and structural CIN (S-CIN), supporting the notion that different mechanisms underlie these processes. This molecular cytogenetic analysis identified a novel reciprocal translocation t(8:12)(p21.3;p13.31) present in all cells of the SCC cell line MS751, indicative of a selective advantage. The rearrangement resulted in two novel fusion genes, PEX5-LPL on der(8) and LPL-PEX5 on der(12). LPL-PEX5 encodes a truncated transcript but PEX5-LPL encodes a full length chimeric protein, comprising the first exon of PEX5 followed by the majority of LPL coding region, and is the most likely candidate for having driven selection of the translocation. Reverse transcription PCR was used to show that LPL is generally expressed at negligible levels in the cervix whereas PEX5 is expressed constitutively. In concordance, PEX5-LPL was expressed at substantially higher levels than LPL-PEX5. The function of PEX5-LPL might be to drive aberrant expression of the 3’ partner or the chimeric protein might have a modified or novel function. Overexpression of LPL relative to normal cervix was found in over one third of cervical SCC cell lines and primary tumour samples, suggesting it is common in cervical SCC. Findings suggest that PEX5-LPL and LPL overexpression have similar roles in cervical carcinogenesis; functional studies of overexpression elucidated a role for both proteins in increased cellular invasion. The functionally important domain might be shared between these proteins and is most likely to be in the C terminal region of LPL. This C terminal domain may be considered as a novel candidate for targeted therapy of cervical SCC.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597332  DOI: Not available
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