Molecular analysis of 1p36 breakpoints in two Merkel cell carcinomas

Abstract

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.

Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma

“…Interestingly, the observed under-and overrepresentations of partial chromosomal regions were quite similar to those observed in small-cell lung carcinoma (SCLC) (Ried et al, 1994;Levin et al, 1995;Petersen et al, 1997;Van Gele et al, 1998). Both are neuroendocrine tumors with remarkable histopathological similarities, that is, small round cells often containing dense core granules and expressing several identical immunohistochemical markers (Ratner et al, 1993;Metz et al, 1998;Schmidt et al, 1998;Goessling et al, 2002).…”

“…In a previous study, we have determined by comparative genomic hybridization (CGH) the patterns of genomic imbalances which occur in MCC (Van Gele et al, 1998). Interestingly, the observed under-and overrepresentations of partial chromosomal regions were quite similar to those observed in small-cell lung carcinoma (SCLC) (Ried et al, 1994;Levin et al, 1995;Petersen et al, 1997;Van Gele et al, 1998).…”

“…T95-45 was established at the Center for Medical Genetics, Ghent, Belgium. Most cell lines were previously analysed by CGH and/or multiplex fluorescence in situ hybridization (Van Gele et al, 1998. Small-cell lung carcinoma cell lines NCI-H69 and NCI-H146 were obtained from the American Type Culture Collection, COR-L88 was a gift from Dr P Twentyman, Cambridge, UK and GLC4 was a gift from Dr Marc Maliepaard, Amsterdam, The Netherlands.…”

Frequent allelic loss at 10q23 but low incidence ofPTEN mutations in merkel cell carcinoma

“…Although cytogenetic findings have been described in about 30 MCCs, no recurrent chromosomal abnormalities have been identified except for loss of distal 1p material due to various types of chromosomal aberrations. Further support for 1p involvement in MCC was provided by Van Gele et al, 5 who showed that 2 distinct regions on 1p36 are implicated in MCC. In the search for chromosomal losses indicating possible involvement of tumorsuppressor genes in MCC, loss of heterozygosity (LOH) studies for markers on 1p, 3p and 13q have been undertaken.…”

Mutation analysis of P73 and TP53 in Merkel cell carcinoma

“…No consistent translocations have been observed but structural abnormalities involving the short arm of chromosome 1 have been noted in 40% of all examined cases. Chromosome region 1p36, which is frequently deleted in a variety of neoplasms including neuroendocrine tumours such as neuroblastoma, is often affected in MCC tumours with 1p rearrangements (Van Gele et al, 1998). Several candidate tumour suppressor genes have been mapped to 1p36 but as yet no direct involvement of these genes in tumours with 1p36 loss could be found (Schwab et al, 1996).…”