Mechanistic study of TFE3 breakage in TFE3-rearranged renal cell carcinoma: the perspective of non-canonical DNA structures and their stability

Our findings indicate that breakpoint events in <i>TFE3</i>-rRCC are non-randomly clustered within intron 5. This clustering correlates strongly with regions characterized by high thermodynamic stability fluctuation (|d<i>ΔG</i>|) of potential non-canonical DNA secondary structures. The principle that elevated local thermodynamic stability fluctuation is a feature of breakpoint locations was supported by analysis of a broader set of oncogenes, suggesting that high local thermodynamic stability fluctuation is a common feature of translocation-prone regions in cancer, representing a plausible, though not proven, contributor to genomic fragility.