Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523409
Title: Epigenetic analysis of childhood leukaemia and the Hippo pathway
Author: Dunwell, Thomas Lawson
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2010
Availability of Full Text:
Access through EThOS:
Full text unavailable from EThOS. Thesis embargoed until 01 Jul 2030
Access through Institution:
Abstract:
Hypermethylation of CpG islands is one of the many processes that a developing cancer cell may use for the inactivation of tumour suppressor genes. The Sav/Hippo/Warts pathway was originally identified in Drosophila and shown to be responsible for controlling both growth and apoptosis, implying this is a tumour suppressor pathway. This pathway is both evolutionarily and functionally conserved in mammals. Work presented here shows that apart from FAT1 and YAP other pathway members are not epigenetically silenced in common epithelial or haematological cancers. FAT1 and YAP were frequently methylated in childhood acute lymphoblastic leukaemia (ALL) but unmethylated in epithelial cancers. Childhood ALL is a blood cancer with peak prevalence between the ages of 3-5 years. The epigenetics of this cancer were examined with three separate approaches; the first, a candidate gene approach, second a NotI restriction enzyme based array examining the methylation of genes residing on chromosome 3, and thirdly the methylated-CpG island recovery assay (MIRA) combined with CpG island arrays examining methylation on a genome-wide scale. These approaches identified a large number of novel genes which were frequently methylated in ALL. Many of the identified genes were new methylation targets and were shown to be likely targets for methylation in both common epithelial and haematological cancers. A series of these genes was seen to be specifically methylated in different leukaemia sub types, and to cluster T-ALL and B-ALL samples into high and low methylation clusters. When examined in chronic lymphoblastic leukaemia (CLL) methylation of two of the above genes was associated with disease progression and methylation of another gene was associated with response to clinical treatment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.523409  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Share: