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Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
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Patched 1 expression in Merkel cell carcinoma
Thilo Gambichler1, Max Dreißigacker1, Dimitri Kasakovski1
1Department of Dermatology, Skin Cancer Center, Ruhr-University Bochum, Bochum, Germany.
The Journal of Dermatology
|November 12, 2020
Summary
Hedgehog signaling molecules like PTCH1 are aberrantly expressed in Merkel cell carcinoma, differing from healthy skin. This dysregulation, potentially driven by GLI, impacts cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Hedgehog signaling's role in Merkel cell carcinoma (MCC) is unclear, with conflicting research.
- Understanding aberrant signaling is crucial for MCC treatment and prognosis.
Purpose of the Study:
- To investigate Hedgehog signaling molecule expression in MCC.
- To identify causes of aberrant expression.
- To correlate findings with patient clinical outcomes.
Main Methods:
- Immunohistochemistry for Sonic, Indian, Patched 1 (PTCH1), and Smoothened on MCC tumor tissue.
- Quantitative real-time PCR for mRNA expression in MCC cell lines.
- PTCH1 sequencing and DNA methylation microarray analysis.
Main Results:
- PTCH1 immunoreactivity in MCC resembles basal cell carcinoma, distinct from healthy skin.
- PTCH1 promoter regions were hypomethylated, independent of gene expression or viral status.
- Differential expression of PTCH1 and GLI genes observed in cell lines, with a GLI2-PTCH1 mRNA correlation.
Conclusions:
- PTCH1 expression in MCC is variable and not solely explained by methylation.
- GLI appears to upregulate PTCH1 as a target gene, suggesting a role in MCC pathogenesis.
- Further research into Hedgehog pathway modulation in MCC is warranted.
Keywords:
Gene expressionHedgehog signalingMerkel cell carcinomaMerkel cell polyomavirusPatched 1 | Gene expression
