MOLECULAR ANALYSIS OF LP36 BREAKPOINTS IN 2 MERKEL CELL CARCINOMAS

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Only little information is available on the genetic alter ations occurring in this tumor. Cytogenetic studies thus far have not shown recurrent chromosomal changes, although various structural chrom osome 1 rearrangements, including deletions, often leading to loss of distal 1 p material appear to be frequent. We report on fluorescence i n situ hybridization and loss of heterozygosity analyses of an MCC tum or and MCC cell line UISO. The present study has shown that two distin ct regions in the most distal band 1p36 on the short arm of chromosome I can be implicated in MCC. One region at 1p36.3 was delineated by a distal deletion in the MCC tumor as a result of an unbalanced transloc ation, resulting in loss of all markers distal to ENO1. This region wa s previously shown to be deleted in different tumor types including ne uroblastoma. In cell line UISO an insertion in 1p36.2 was identified. The insertion breakpoint indicates a second, more proximal, region on Ip involved in MCC. The insertion breakpoint was mapped within a clust er of repetitive tRNA and snRNA genes and thus could coincide with the constitutional 1p36 breakpoint previously reported in a patient with neuroblastoma. (C) 1998 Wiley-Liss, Inc.