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1.  Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc 
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high-resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10 and 13. MCC tumors with less genomic aberration were associated with improved survival (p=0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26% of tumors, a deletion of 13q14-21 was recurrent in 26% of tumors and contains the well-characterized tumor suppressor RB1, and a novel focal amplification at 1p34 was present in 39% of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, while 4/4 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.
doi:10.1038/jid.2008.365
PMCID: PMC2830552  PMID: 19020549
Merkel cell carcinoma; comparative genomic hybridization; L-Myc; Merkel cell polyomavirus; genetics
2.  Does a new polyomavirus contribute to Merkel cell carcinoma? 
Genome Biology  2008;9(6):228.
A new polyomavirus has been discovered in Merkel cell carcinomas, but does it contribute to carcinogenesis?
A new technique designed to hunt for non-human transcripts has identified a novel SV40-like virus present in the majority of Merkel cell carcinomas. Here we examine what it will take to determine whether or not this virus contributes to carcinogenesis.
doi:10.1186/gb-2008-9-6-228
PMCID: PMC2481414  PMID: 18598371
4.  Merkel cell carcinoma adjuvant therapy: Current data support radiation but not chemotherapy 
Merkel cell carcinoma is a skin cancer with 30% mortality and an incidence that has tripled in the past 15 years. There is agreement that surgical excision with negative margins is an appropriate therapeutic first step and that sentinel lymph node biopsy is a powerful prognostic indicator. Following excision of detectable cancer, optimal adjuvant therapy is not well established. A role for adjuvant radiotherapy is increasingly supported by retrospective data suggesting a nearly four-fold decrease in local recurrences if radiation is added to surgery. In contrast, a role for adjuvant chemotherapy is not well supported. The rationale for chemotherapy in this disease is based on small-cell lung cancer, a more common neuroendocrine tumor for which chemotherapy is the primary treatment modality. Several issues call into question the routine use of adjuvant chemotherapy in Merkel cell carcinoma: lack of evidence for improved survival; the associated morbidity and mortality; important differences between small-cell lung cancer and Merkel cell carcinoma; and rapid development of resistance to chemotherapy. Importantly, chemotherapy suppresses immune function that plays an unusually large role in defending the host from the development and progression of Merkel cell carcinoma. Taken together, these arguments suggest that adjuvant chemotherapy for Merkel cell carcinoma patients should largely be restricted to clinical trials.
Merkel cell carcinoma is a neuroendocrine cancer that typically presents as a rapidly growing non-specific nodule on sun exposed skin in people over 65 years of age. The recent increase in incidence to over 1000 cases a year in the United States has led Merkel cell carcinoma to become the second most common cause of non-melanoma skin cancer death.1,2 Optimal management for Merkel cell carcinoma beyond surgical excision is not agreed on, and no randomized trials have been carried out. Sentinel lymph node biopsy has been shown to be powerful in predicting subsequent recurrences as well as in determining if further nodal treatment is indicated.3,4
doi:10.1016/j.jaad.2007.03.011
PMCID: PMC1950220  PMID: 17482714

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