Molecular Genetic Mechanisms in Cancers of Keratinocytic Origin

Abstract

Keratinocytic cancers (KC) comprise a group of diseases that have a broad spectrum clinically and pathologically. At one end of the spectrum are benign proliferations (acanthomas), and at the other end are malignant tumors with aggressive growth and metastatic potential. Traditionally, about 80% of KC cases have basal cell carcinoma (BCC) and 20% have cutaneous squamous cell carcinoma (cSCC). Both tumors have different phenotypic features due to different oncogenic pathways. cSCC is biologically different and requires a different approach due to the higher risk of local recurrence, metastasis and death. Genetic factors play an important role in the development of KC. Family and family history studies, the presence of KC as a feature of rare hereditary syndromes, and genetic association studies give us clues in this regard. More than 20 genetic syndromes associated with KC have been described. Some syndromes are associated with multiple BCC, some with multiple cSCC, and some with both BCC and cSCC. Environmental risk factors include exposure to ultraviolet light radiation and immunosuppression in both tumors. Exposure to ionizing radiation is most common in BCC, while smoking and photosensitive drug use are among the environmental risk factors for cSCC. Molecular, epidemiological, and clinical studies will help better understand the cellular processes involved in tumorigenesis, and develop new strategies for treating and preventing KCs.