MICROSATELLITE INSTABILITY IN HUMAN NONMELANOMA AND MELANOMA SKIN-CANCER

Microsatellite instability secondary to replication errors (RER), char acterized by length changes at repetitive loci scattered throughout th e genome, is a recently recognized genetic mechanism important in the development of some human cancers, Although RER has been reported in s ebaceous gland tumors from patients with the Muir-Torre syndrome, the frequency of RER in human non-melanoma and melanoma skin cancers is no t known, In this study, we investigated the importance of RER in human skin carcinogenesis. RER was identified in three of four actinic kera toses from a patient belonging to a kindred with documented Muir-Torre syndrome, which indicates that defective DNA replication may contribu te to skin cancer development in such patients, Examination of a serie s of tumors from patients without Muir-Torre, including 137 skin cance rs (47 basal cell carcinomas, 49 squamous cell carcinomas, and 41 prim ary malignant melanomas), 19 actinic keratoses, and 20 cases of Bowen' s disease, using 10 or more microsatellite markers, identified repeat- sequence instability in less than 5% of the tumors studied, In six of the eight tumors, the sole change was an alteration 2 base pairs in le ngth at a single locus, One patient with a squamous cell carcinoma sho wed changes at multiple loci suggesting defective mismatch repair, Alt hough the low frequency of RER found in this study of a large series o f human skin tumors suggests that this phenomenon is uncommon in patie nts with skin cancer, the identification of RER at multiple loci in tw o patients suggests that error-prone replication may be important in s kin cancer development in some individuals,