期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 133, 期 4, 页码 936-945出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2012.445
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资金
- Anatomic Pathology Project Fund of the University of Michigan Department of Pathology
- Dermatology Foundation
- Training Grant in Cell and Molecular Dermatology [T32AR007197]
- NIH [R01CA087837]
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCCs, may drive tumorigenesis via viral T antigens. However, the mechanisms underlying pathogenesis in MCPyV-negative MCCs remain poorly understood. To nominate genes contributing to the pathogenesis of MCPyV-negative MCCs, we performed DNA microarray analysis on 30 MCCs. The MCPyV status of MCCs was determined by PCR for viral DNA and RNA. A total of 1,593 probe sets were differentially expressed between MCPyV-negative and MCPyV-positive MCCs, with significant differential expression defined as at least a 2-fold change in either direction and a P-value <= 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may have an important role in the tumorigenesis of MCPyV-negative MCCs. Functional and clinical validation studies are needed to determine whether this tumor-suppressor pathway represents an avenue for targeted therapy. Journal of Investigative Dermatology (2013) 133, 936-945; doi:10.1038/jid.2012.445; published online 6 December 2012
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