SPEN and in situ carcinoma: We further established relative timing of SNVs in several lower-prevalence driver genes (in order of increasing mRT): FBXW7, NOTCH1, CASP8, FAT1, NSD1, HRAS, EP300, CREBBP, KMT2D, PIK3CA, NFE2L2, HLA-A, SPEN and KMT2C. mRT values of events in the first nine genes were less than 0.69, supporting early roles in tumorigenesis before carcinoma in situ.