© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1103-1109, Copyright © 1997 by Oxford University Press
MR Gailani and AE Bale
Many genes originally identified because of their role in embryonic
development are also important in postnatal control of cell growth and
differentiation. Mutations in some of these genes have been shown to cause
cancer. Basal cell carcinoma (BCC) of the skin is the most common cancer in
humans. More than 750000 new cases are diagnosed annually, and the
incidence is rising. BCCs are slow-growing, locally invasive tumors that
rarely metastasize but can result in extensive morbidity through local
recurrence and tissue destruction. Epidemiologic studies suggest that
sunlight (particularly UVB radiation) is a strong risk factor for BCC
formation, although other factors are also involved. The nevoid basal cell
carcinoma syndrome (NBCCS), a rare genetic disorder, is characterized by
predisposition to BCCs and other tumors as well as to a wide range of
developmental defects. NBCCS maps to chromosome 9q22.3, and loss of
heterozygosity at this site in both sporadic and hereditary BCCs suggests
that it functions as a tumor suppressor. The gene for NBCCS was recently
cloned and is the human homologue of the Drosophila gene "patched." Genetic
studies in Drosophila show that patched is part of the hedgehog signaling
pathway, which is important in determining embryonic patterning and cell
fate in multiple structures of the developing embryo. Human patched is
mutated in both hereditary and sporadic BCCs, and inactivation of this gene
is probably a necessary, if not sufficient, step for BCC formation.
Delineation of the biochemical pathway in which patched functions may lead
to rational medical therapy for BCCs and possibly for other tumors
associated with NBCCS.
REVIEWS
Developmental genes and cancer: role of patched in basal cell carcinoma of the skin
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA. mae_gailani@yale.edu
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