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Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Only little information is available on the genetic alterations occurring in this tumor. Cytogenetic studies thus far have not shown recurrent chromosomal changes, although various structural chromosome 1 rearrangements, including deletions, often leading to loss of distal 1p material appear to be frequent. We report on fluorescence in situ hybridization and loss of heterozygosity analyses of an MCC tumor and MCC cell line UISO. The present study has shown that two distinct regions in the most distal band 1p36 on the short arm of chromosome 1 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 translocation, resulting in loss of all markers distal to ENO1. This region was previously shown to be deleted in different tumor types including neuroblastoma. In cell line UISO an insertion in 1p36.2 was identified. The insertion breakpoint indicates a second, more proximal, region on 1p involved in MCC. The insertion breakpoint was mapped within a cluster of repetitive tRNA and snRNA genes and thus could coincide with the constitutional 1p36 breakpoint previously reported in a patient with neuroblastoma. Genes Chromosomes Cancer 23:67–71, 1998. © 1998 Wiley‐Liss, Inc.

Adenovirus type 12 (Ad12) induces gaps at chromosomal bands 1p36, 1q21, 1q42-43 and 17q21 after infection of human embryonic kidney cells. Three of these bands harbour small nuclear RNA genes or pseudogenes, but the study of a possible relationship has been hampered by the lytic character of adenovirus infection. A non-lytic Ad5/SV40 hybrid virus preferentially integrates at 1p36 and the integration site has been cloned. Chromosomal band 1p36 encodes genes for small nuclear RNA U1 (RNU-1) and for the tRNAs of glutamic acid (TRE) and asparagine (TRN). Each of these genes is encoded by 15-30 copies. We studied the organization of these genes and of the viral integration site by pulsed field gel electrophoresis (PFGE) and analysis of yeast artificial chromosomes (YACs). We show that RNU-1, TRE and TRN genes are scattered over a region of probably more than 2 Mb with intergenic distances of up to 125 kb. The Ad5/SV40 integration site maps to identical chromosomal NotI fragments as RNU-1 and TRE. Fine mapping of a YAC shows that the integration site is within 40-70 kb of genes for RNU-1, TRN and TRE.

We have constructed a 1.4-Mb P1 artificial chromosome/bacterial artificial chromosome (PAC/BAC) contig spanning the 17q breakpoint of a constitutional translocation t(1;17)(p36.2;q11.2) in a patient with neuroblastoma. Three 17q breakpoint-overlapping cosmids were identified and sequenced. No coding sequences were found in the immediate proximity of the 17q breakpoint. The PAC/BAC contig covers the region between the proximally located ACCN1 gene and the distally located TLK2 gene and SCYA chemokine gene cluster. The observation that the 17q breakpoint region could not be detected in any of the screened yeast artificial chromosome libraries and the localization of the 17q breakpoint in the vicinity of the distal breakpoints of two microdeletions in patients with neurofibromatosis type 1 suggest that this chromosomal region is genetically unstable and prone to rearrangements.