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Title: Molecular genetic analysis of oligodendroglial tumours
Author: Chan, R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2009
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96 Oligodendroglial gliomas were first studied by a genome-wide 1Mb array-CGH followed by analysis using chromosome 7 and 10 tile-path and regional tile-path arrays to more exactly define the extent of copy number aberrations. This strategy allowed the identification of several novel amplifications and homozygous deletions (HD). A comparative survival analysis for the groups of patients defined by unsupervised hierarchical clustering of the 1Mb array data as well as histopathological diagnosis, 1p/19q status and Tp53 mutation were performed. At least four distinct subgroups were identified: two groups with 1p/19q total loss and two groups without, exhibiting distinct genetic profiles and survival. Some individual genomic region abnormalities also correlated with survival. A number of these are novel. While total loss of 19q was the most predominant pattern in oligodendroglial tumours, astrocytic tumours had complex patterns of partial deletions, grains, trisomy or monosomy of chromosome 19. This suggests that there may be several astrocytoma relevant regions on chromosome 19. A novel candidate tumour suppressor gene (TSG) region at 19q13.41 was delineated in the astrocytic tumours. A rare novel somatic homozygous deletion in the kallikrein gene cluster region was identified in one oligodendroglioma. To explore the potential breakpoints of the t(1;19) translocation on 19q, gliomas with 1p/19q total losses were screened. The findings indicate the existence of several recurrent breakpoints in the gene-depleted pericentrometric region of 19q. Other novel findings include 3 tumours with 1p/19q deletions that had HDS of PTPRD on 9p23-9p24.1. These deletions affected only the 5’UTR of the long isoforms of PTPRD. No somatic mutations affecting the coding sequence, aberrant methylation of the gene or significantly altered mRNA expression levels were observed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available