Paul Edwards - Overview

Chromosome rearrangements-translocations, inversions, deletions and so on-are frequent in common cancers such as breast, colorectal and ovarian carcinoma. A typical breast cancer, for example, will have 10 to 20 chromosome aberrations. These aberrations are almost certainly an important source of gene changes driving the cancers, yet we know very little about them. Recent developments in fluorescence staining of chromosomes-fluorescence-in situ hybridisation or FISH-now make it possible to analyse the rearrangements accurately. Our research is aimed at cataloguing the chromosome aberrations in common cancers, particularly breast cancer, to look for common patterns of rearrangement. In particular we are searching for recurring breakpoints, i.e. small regions of a chromosome where breaks occur in several cases of the same type of tumour. We have already described one such recurrent break, on the short arm of chromosome 8. Such breaks are likely to affect genes located close to the break, and may lead us to genes that are altered in these cancers, giving insight into the mechanisms of malignancy and possible new targets for therapy. In addition to individual chromosome aberrations, different tumours seem to exhibit different mechanisms of generating chromosome aberration, leading to different overall patterns of karyotype. For example, some tumours seem to preferentially lose chromosomes, while others accumulate additional chromosomes or chromosome fragments. Other cases show a high frequency of reciprocal translocations. The underlying cause is probably different kinds of genomic instability in the tumours, which probably also relates to responses to traditional cytotoxic therapies.