As HR-related gene mutation is considered a compensatory event following PTEN-deficiency22, these findings imply that HR repair activity was sequentially shifted together with mutation accumulation after the occurrence of aberrant PTEN. Although POLE category tumours predominantly indicated the presence of Signature.10 based on deconstructSigs14, Signature.3 representing double-strand breaks was rare in these tumours (data not shown), suggesting that HR function may be gradually restored after occurrence of PTEN mutation. Here, PTEN is linked to neoplasm.