MIG Seminar – Colin Semple – 9th February, 2018
MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, UK
Friday 9th February
FW Jones Theatre, Medical Building, The University of Melbourne
Breaking point: computational interrogation of structural variation in cancer
Structural variants (SVs) are known to play important roles in a wide variety of cancers, but their mutational origins and functional consequences are still poorly understood. The highly nonrandom distributions of these variants across tumour genomes are often assumed to reflect selective processes, but mutation rates can vary by orders of magnitude and often reflect the underlying chromatin structure at a locus. The prediction of SVs under selection for enhanced tumourigenesis therefore remains challenging, though identifying such variants may lead to new diagnostic and therapeutic targets. We have adopted a modelling approach to predict the susceptibility of a genomic region to the mutations leading to SVs. Then by reconciling the frequency of SVs observed in a tumour type with the expected frequency, given the model, we infer ‘hot' and ‘cold’ spot regions harbouring unexpectedly high or low rates of SVs respectively. These regions show intriguing enrichments of genes and regulatory elements and we suggest they are likely to be subject to selection in tumours.
Enquiries: Andrew Siebel (email@example.com)