Deletion mapping of the short arm of chromosome 3 in Merkel cell carcinoma.
Little is known about the biology of Merkel cell carcinoma (MCC), also called small cell carcinoma of the skin. MCC has similarities with small cell lung cancer (SCLC): both are neuroendocrine malignancies with early metastasis to distant sites and a poor prognosis. Small cell lung cancer biopsies are known to have frequent losses on chromosome 3 in the region 3p21, yet MCCs have not been reported to have 3p deletions by karyotypic analysis. Considering the similarities between SCLC and MCC, we investigated 26 MCC tumours for loss of heterozygosity (LOH) on 3p. First, RFLP analysis was performed using PCR with nine primer sets from six loci. Second, 25 tumours were examined by microsatellite analysis for 3p markers D3S1289 and D3S1285 and SST on 3q. All 26 tumours were informative at one or more loci; of these, 18 (69%) demonstrated LOH for at least one marker on the short arm. For all informative loci the frequency of LOH was greater than 30% (range 33-75%). In a cell line derived from one tumour, it was possible to demonstrate rearrangement of chromosome 3 by in situ hybridisation. No LOH was seen in 15 informative cases for the 3q locus SST. A region 3p13-p21.1, centered on the marker D3S2, was deleted in all tumours demonstrating LOH, with a secondary deletion involving D3S30 detected in some tumours at 3p13. Our results indicate that LOH on 3p is a common occurrence in MCC; however, three tumours for which DNA was also available from a corresponding cell line suggest there may be a subset of MCC whose genesis is independent of deletions of 3p.
Leonard
J H
JH
Queensland Radium Institute Laboratory, Queensland Institute of Medical Research, Australia.
Williams
G
G
Walters
M K
MK
Nancarrow
D J
DJ
Rabbitts
P H
PH
D015266:Carcinoma, Merkel Cell / Q000235:genetics*; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics* / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000235:genetics; D004854:Herpesvirus 4, Human; D006801:Humans; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000235:genetics* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm