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Loss of Heterozygosity for 10q22-10qter in Malignant Melanoma Progression¹

Ludwig Institute for Cancer Research [R. A. H., W. K. C., K. C. A.], Center for Molecular Genetics [W. K. C.], and Department of Medicine [W. K. C., K. C. A.], University of California at San Diego, La Jolla, California 92093-0660, and the Hautklinik Mannheim, Fakultät für Klinische Medizin Mannheim der Ruprecht-Karls-Universität Heidelberg, Mannheim, D 68135, Germany [R. A. H., J. W., A. E.]

Karyotypic and molecular data indicate that genetic events involving the chromosome region 10q22-10qter may be related to tumorigenesis in malignant melanoma. To test this we analyzed 10 polymorphic microsatellite repeats in the region 10q22-qter, using a polymerase chain reaction-based assay for loss of heterozygosity and DNA isolated from normal and tumor tissue from 26 individuals with malignant melanoma. The samples included 19 paired normal and malignant tissues representing various stages of melanoma as well as 7 cases in which samples from at least 2 different points in time during tumor progression were available. Our findings indicate that loss of heterozygosity of 10q22-10qter is a frequent event, that the observed loss of heterozygosity does not result from whole chromosome loss, and that it is associated with tumor progression. Finally, the appearance of new alleles in two of the tumors may indicate the involvement of DNA replication errors in melanoma analogous to such events in other tumor types.

¹ Supported in part by the Deutsche Forschungsgemeinschaft (Grant He 2228/1-1 to R. A. H.), the Deutsche Krebsforschungszentrum, and the Verein zur Förderung dermatologischer Forschung e.V., Mannheim.

² To whom requests for reprints should be addressed, at the Ludwig Institute for Cancer Research, San Diego Branch, 9500 Gilman Drive, La Jolla, CA 92093-0660.

Received 3/10/94. Accepted 5/ 3/94.

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