Since the number of variants in a tumor can by influenced strongly by hypermutation we stratified the tumors using a mutational signature analysis12, and categorized each tumor into one of six categories: non-hypermutated, APOBEC (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like), Smoking-associated, MMR (mismatch repair), UV (ultraviolet), and POLE (DNA Polymerase Epsilon, Catalytic Subunit). Here, POLE is linked to neoplasm.