Claire Dearden BSc, M.D., FRCP, FPCPath Royal Marsden Hospital/ Institute of Cancer Research (United Kingdom)

GENETICS

A study of the poor prognostic genomic alterations affecting 11q and 17p in CLL using CGH arrays

Update:

Prognostic markers in CLL are becoming increasingly important for patients and clinicians alike. Cytogenetic markers, such as 17p deletion, are associated with a very poor outcome in CLL, and, over the grant period, we have examined, in detail, samples from patients in the LRF CLL4 clinical trial in the U.K. In samples with a known 17p abnormality, we used a technique to look for changes in other genes.

We identified highly significant changes in other chromosomes which are associated with the 17p abnormality and may therefore be involved in the development of high-risk disease. In addition, we have also examined what happens to the copy of the gene remaining on the non-deleted chromosome. We have shown that, in the majority of cases, there is a mutation in this remaining copy.

This explains why the TP53 gene is not active in cases with the 17p abnormality and why there is a strong association with resistance to chemotherapy which is dependent on a functional TP53 pathway for activity. These results have helped further our understanding of the reasons behind the poor outcome for patients with these specific genetic changes.