Understanding spontaneous loss of heterozygosity
Worldwide Cancer Research
Institute Curie
Using a novel model established in my team of spontaneous stem cell genome instability in fruit flies, our proposed work will address several important currently open questions about a major pathway of tumor suppressor inactivation: loss of heterozygosity via mitotic recombination. How do genomic features contribute to initiation of mitotic recombination? What tissue-intrinsic and extrinsic factors contribute to LOH initiation and neoplastic growth? We will explore these questions using whole-genome sequencing approaches combined with sophisticated Drosophila genetics. Our findings will bring to light mechanisms that are at work in vivo in adult stem cells and have numerous implications both for basic science as well as potential future preventative measures for patients.
2.1 Biological and endogenous factors