Expanded Structural Variant Signatures and Their Role in Predicting Chemotherapy Sensitivity.

Cancer cells harbor scrambled genomes – their DNA resembles a choose-your-own adventure book, but without the instructions of which page to turn to next. In fact, these structural variants (SVs) affect a larger fraction of the cancer genome than any other type of mutation in cancer, but they have been less well studied due to technical challenges in detection and analysis. Different cancers exhibit different patterns of SVs, and these SV signatures can serve both as a window into the mechanisms by which DNA is damaged and defects in the ways in which different types of cancer cells repair their damaged DNA. SV signatures can also serve as biomarkers that indicate whether a cancer is likely to respond to different treatment approaches. Indeed, many of our cancer treatments work by damaging DNA, so these signatures—which indicate how different cancers respond to that damage—are very salient. We are improving methods to detect these SV signatures and systematically evaluating the relationships between SV signatures and sensitivity to a variety of cancer treatments. Our work, which will be made available to the scientific community, will result in new insights into the DNA damage and repair defects that underly various cancers and in SV-based biomarkers of sensitivity to treatments that may be tested in clinical trials.