Translocation Affecting Sonic Hedgehog Genes in Basal-Cell Carcinoma

The sonic hedgehog (SHH) pathway is activated in basal-cell carcinoma, and loss-of-function mutations in SHH cause holoprosencephaly. This study uncovers a translocation involving the SHH promoter in a person with holoprosencephaly and basal-cell carcinomas. To the Editor: The sonic hedgehog (SHH) signaling pathway plays an essential role during human development, and its dysregulation causes developmental defects such as holoprosencephaly and a variety of human cancers, including basal-cell carcinomas. 1 Although mutations in patched homologue 1 ( PTCH1 ) and smoothened homologue ( SMO ) encoding the receptors PTCH1 and SMO, respectively, are known to predispose to inherited and sporadic basal-cell carcinomas, up-regulation of hedgehog ligands such as sonic hedgehog have been associated with lethal tumors such as pancreatic or lung cancer. Here, we describe a person with overexpression of SHH and widespread and aggressive basal-cell . . .