Microsatellite instability in malignant melanomas

Abstract

Microsatellite instability (MSI) is caused by deficient DNA mismatch repair, and results in a "mutator" phenotype. Recent studies have produced contradictory results about the frequency and significance of MSI in malignant melanomas. In this study, we therefore determined the time of onset and relative frequency of MSI during the progression of melanocytic tumours, including benign melanocytic naevi. We examined 7 different microsatellite loci in 9 melanocytic naevi, 25 primary malignant melanomas and 8 melanoma metastases. None of the melanocytic naevi showed MSI. In contrast, moderate frequency of MSI in 1/12 (8%) was detected in thin melanomas of <0.75 mm vertical thickness and in 1/8 (12%) of those with a thickness >0.75 mm and < 1.5 mm. The rate of MSI was increased in tumours thicker than 1.5 mm (2/5) and in melanoma metastases, with over 25% (2/8) of the lesions investigated. We conclude that MSI occurs in a considerable subset of malignant melanomas and that there is a pattern consistent with increasing frequency of MSI with progression of melanocytic tumours.