Gene interactions in cancer

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

1. We have previous published a paper in Cell Reports where, where we generalize the concept of synthetic lethality, and comprehensively identify clinically relevant gene interactions of 12 distinct types (SL being one of them). In collaboration with Aldape lab, are now extending the notion of gene interactions to interactions between specific states of specific cell types (for instance, cytotoxic T cells and mesenchymal malignant cells) with goal of specifically identifying functional interactions between specific processes/states across cell types. The project is ongoing. 2. Gene signature refers to a set of genes whose expression characterizes the activity of a specific biological process or a cell state, e.g., EMT, proliferation, stemness, etc. Gene signatures are widely used to infer the state of a biological system based on transcriptomic data. However, the available gene signatures lack tissue or cellular context. For instance, a stemness signature derived from one tissue context may not be perfectly applicable to another tissue context. Across tissues, overlapping, yet distinct, sets of genes are likely to mediate a specific biological process. In a new project, we aim to derive cancer type-specific gene signatures, initially for 14 oncogenic hallmark processes across 23 cancer types, by integrating the available context-agnostic gene signatures with the protein interaction network and cancer-specific transcriptomic data. Our preliminary results suggest that for several hallmarks, most notably DNA Damage, DNA Repair, and EMT the derived tissue-specific gene signatures are significantly more prognostic of survival in the corresponding cancer than the context-agnostic signatures.