What is the molecular basis for the development of sporadic basal cell carcinoma?

The best evidence suggests that the majority of sporadic BCCs are the result of ultraviolet (UV)-induced alterations in the hedgehog signaling pathway. The most common mutation in sporadic BCCs (90%) occurs in the tumor suppressor gene PTCH, found at locus 9q22, that encodes the Ptch1 protein. This protein is a receptor for a secreted protein ligand called sonic hedgehog (Shh), which is important in signaling processes that control cell growth and fate. Another 10% of sporadic BCCs have activating mutations in the smoothened protein (SMO), another participant in the hedgehog signaling pathway. Investigation into this pathway has led to the development of a small molecule inhibitor of the hedgehog pathway called GDC-0449 that shows promise in the treatment of locally advanced and metastatic BCC.

Epstein EH: Basal cell carcinomas: attack of the hedgehog, Nat Rev Cancer 8(10):743–754, 2008.

Von Hoff DD, LoRusso PM, Rudin CM, et al: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma, N Engl J Med 361(12):1164–1172, 2009.