"S-associated malignancies is thought to arise from the classic two-hit suppressor gene model: baseline heterozygosity secondary to germline PTCH mutation as the first hit, with the second hit due to mutagen exposure such as UV or ionizing radiation.[63,64,65,66,67] However, haploinsufficiency or dominant negative isoforms have also been implicated for the inactivation of PTCH1.[68]" . . . .