POLE and neoplasm: Moreover, they present a characteristic variant spectrum, enriched in C > A transversions in the context of TCT, and C > T transitions in the context TCG [15, 21], which corresponds to tumor mutational signatures SBS10a, SBS10b, and SBS28 [22] for Polε proofreading defects, and SBS10d and SBS10c (identified in unaffected tissues) for Polδ proofreading deficiency, of the Catalogue Of Somatic Mutations In Cancer (COSMIC) (https://cancer.sanger.ac.uk/signatures/sbs/Mutational Signatures v3.2) [21, 23].