Characterization of chromosomal instability-related dependencies through cell-specific metric for gene dosage compensation potential

Numerical chromosomal instability (n-CIN) is a defining characteristic of most human cancers with serious implications of large-scale alterations of the genome – such as chromosome arm level copy number changes. These kinds of somatic alterations are frequently targeting oncogenes and tumor suppressors, enriched in cancer driver events in order to shape the transcriptome in favor of tumor progression and proliferation. While oncogenes are mostly associated with copy number gains and tumor suppressors are more frequent in chromosome arm losses, neighboring genes are also affected in both cases. This collateral damage may be able to create synthetic lethal relationships and context-specific dependencies. Cancer cells might be able to avoid partial loss and gain-related lethal effects by triggering different dose compensation mechanisms, occurring at the genomic, epigenetic and post-translational levels, which leads to deviations across copy number and expression profiles.