The progression of a cell from normal function to the unchecked replication observed in malignant cancers is advanced by various environmental or internal processes which damage cellular DNA. Whether DNA damage is a “first-mover” causative agent or a secondary step in a cascade of cellular processes differs from case to case. Damage to DNA’s integrity, however, is common to all cancers and many diseases in general. Modification sites on polynucleotides, commonly referred to as lesions, often take the form of minor changes in the molecular structure or conformation of the nucleobase. Locating these changes in the DNA sequence of single molecules is difficult because they largely cannot be assayed by conventional sequencing techniques. A potentially powerful solution to this problem is offered by the TERS technique, which conventionally provides resolutions on the order of 10 nm, but whose resolution, in theory, can be improved to the single-base stacking distance by utilizing principles of super-resolution.
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