Department of Pathology

Professor Peter Collins

Research description

The group is focusing on human brain tumours. Brain tumours are responsible for 7% of the years of life lost from cancer before the age of 70 (www.cancerresearchuk.org). The studies presently aim at documenting the genetic abnormalities that are involved in the development of these tumours and how these affect cell function. The ultimate aim is to identify prognostic markers, markers indicating the most appropriate conventional therapies and finally to identify targets for innovative molecular therapies.

The preliminary genetic analysis is carried out using microarray Comparative Genomic Hybridization (array-CGH) to identify and map regions of the genome consistently lost, gained or amplified at a resolution of a few hundred kilobases. We have in- house produced an array in which clones are spaced on average less than 1Mb interval for the whole human genome (1Mb array, figure) as well as several chromosomal tile path arrays (e.g., chromosome 1, 6, 7, 10, 17, 19 and 22), which cover entire single chromosomes with overlapping clones. Array-CGH analysis is followed by a detailed mapping of the deleted/gained/amplified regions using custom-designed oligonucleotide arrays to identify the potential gene targets of these events.

An overview of the transcriptosome in brain tumours is presently being produced using Affymetrix GeneChips. A genome- wide analysis of CpG island hypermethylation is being investigated using the MeDIP technology. Mutation, methylation and/or expression analysis may then be undertaken, if indicated, to identify the genes involved, using direct sequencing, pyrosequencing or real-time quantitative PCR. Currently a number of potential oncogenes/tumour suppressor genes in regions of the genome consistently amplified, rearranged or lost are being investigated. The data will be analysed in a cell biological framework. As we have extensive clinical data and more than 9 years follow up in all cases, the data can be correlated with the clinical findings.