Cellular Defenses Against Radiation-Induced Carcinogenesis:

Gorlin Syndrome
• Nevoid basal cell carcinoma syndrome (NBCCS)
• Autosomal dominant disease with high penetrance
• Accounts for ~0.5% of all BCC cases (probably much higher
percentage of early onset BCC)
• 20% of the patients also develop medulloblastoma
and other cancers.
• Patients treated with radiotherapy develop large numbers
of basal cell carcinomas in the radiation field.
• Gene responsible is the human homolog of the “Patched”
gene (PTCH) in Drosophila, and may be a tumor suppressor
in mammalian cells.
• Patched is a transmembrane signal transduction protein upstream
of sonic hedgehog, Smoothened, and the proto-oncogene Gli1.
• PTCH heterozygote mice have enhanced sensitivity to radiationinduced
teratogenesis.
NCI REB Radiation Epidemiology Course, May 14, 2007
TJJ