Stephan Stilgenbauer, M.D. University of Ulm (Germany)

GENETICS

Whole genome sequencing to identify pathogenic principles, refine risk stratification, and discover therapeutic targets in CLL

Grant Awarded in 2011

Abstract:

All cancers show abnormalities in their genetic code which contribute to the development of cancer and its clinical course. Each cell is exposed to external and toxic stress and suffers mutations or “mistakes” in the copying process of the genetic code, which will change the cell’s genome. While most of these mistakes will be silent or repaired, some of these mistakes alter critical genes, leading to a growth of cancer cells. There are several different genes which can be altered. This leads to various types and subtypes of cancer. The identification of genes that lead to aggressive disease or resistance to therapy is a central aim of cancer research. While mutations of key tumor suppressors (genes that normally prevent cancer formation; e.g. ATM, TP53) are known, a precise map of mutations of the CLL genome is currently missing.

We hypothesize that critical genes are targeted by mutations during the disease course and lead to particular disease characteristics. Novel methods of analyzing samples will allow us to decipher the genetic code of CLL to understand which changes are driving refractory CLL. Modern sequencing technology holds potential to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks. These insights will identify the mutational signatures associated with different disease courses of CLL. We thus hope to answer key clinical questions necessary to move CLL research forward.