1. ¹Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki, Finland
2. ²Laboratorio de Citogenética y Cátedra de Citología, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, La Plata, Argentina
3. ³Department of Pathology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
4. ⁴Department of Plastic Surgery, Helsinki University Hospital Helsinki, Finland

Correspondence: S Knuutila, Department of Medical Genetics, University of Helsinki, PO Box 21 (Haartmaninkatu 3, 4th floor), Helsinki FIN-00014, Finland. E-mail: sakari.knuutila@helsinki.fi

^*Equal contribution.

Received 9 October 2003; Revised 31 December 2003; Accepted 31 December 2003; Published online 5 March 2004.

Abstract

Comparative genomic hybridization (CGH) was used to search for gains, high-level amplifications and losses of DNA sequences along all chromosome arms in 19 primary Merkel cell carcinomas (MCC). Extensive genetic aberrations, with a mean value of 5.51.1 changes per tumor were detected in 13 out of the 19 samples analyzed. Our CGH results reveal several new and other previously known chromosomal regions that are involved in the pathogenesis of MCC. The majority of the alterations were gains of whole chromosomes or whole chromosome arms. Compared to losses, the frequency of DNA copy number gains was two-fold. DNA sequence copy number gains were most common in chromosomes 6 (42%), 1 (37%), and 5 (32%). The most frequent minimal common regions of gains were 6pterqter (42%), 1q11q31 (32%), and 5p (32%). No recurrent high-level amplifications were observed. High-level amplifications of small chromosomal regions were found in four samples out of the 19 tumors analyzed (21%). Amplifications affected 1q22q24 (5%), 4p (5%), and 5p (5%). Losses most frequently affected chromosomes 13 (21%) and 4 (16%). Minimal common regions with the most frequent losses were 13q13q31 (21%), 4q (16%), and 16q (11%). No significant statistical correlation between genomic aberrations and clinicopathological factors was revealed, despite the fact that there was an obvious tendency towards it. Primary MCC expressing DNA alterations were predominantly distinguished in large tumors, and risk of metastatic dissemination was three-fold compared to tumors with no DNA alterations.