Are there multiple cells of origin of Merkel cell carcinoma?

J. C. Sunshine, N. S. Jahchan, J. Sage, Jaehyuk Choi*

*Corresponding author for this work

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology. Importantly, dramatic differences in the genetics of these two MCC subtypes suggest fundamental differences in their pathophysiology. We review these recent works and find that they provocatively suggest that MCPyV-positive and MCPyV-negative MCCs arise from two different cells of origin: The MCPyV-negative MCC from epidermal keratinocytes and the MCPyV-positive MCC from dermal fibroblasts. If true, this would represent the first cancer that we are aware of that evolves from cells of origin from two distinct germ layers: MCPyV-negative MCCs from ectodermal keratinocytes and MCPyV-positive MCCs from mesodermal fibroblasts. Future epigenetic experiments may prove valuable in confirming these distinct lineages for these MCC subtypes, especially for the clinical importance the cell of origin has on MCC treatment and prevention.

Original languageEnglish (US)
Pages (from-to)1409-1416
Number of pages8
JournalOncogene
Volume37
Issue number11
DOIs
StatePublished - Mar 1 2018

Fingerprint

Merkel cell polyomavirus
Merkel Cell Carcinoma
Keratinocytes
Neoplasms
Fibroblasts
Germ Layers
Virology
Skin Neoplasms
Genomics
Epigenomics
Viruses
Skin
Mortality

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sunshine, J. C. ; Jahchan, N. S. ; Sage, J. ; Choi, Jaehyuk. / Are there multiple cells of origin of Merkel cell carcinoma?. In: Oncogene. 2018 ; Vol. 37, No. 11. pp. 1409-1416.
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title = "Are there multiple cells of origin of Merkel cell carcinoma?",
abstract = "Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology. Importantly, dramatic differences in the genetics of these two MCC subtypes suggest fundamental differences in their pathophysiology. We review these recent works and find that they provocatively suggest that MCPyV-positive and MCPyV-negative MCCs arise from two different cells of origin: The MCPyV-negative MCC from epidermal keratinocytes and the MCPyV-positive MCC from dermal fibroblasts. If true, this would represent the first cancer that we are aware of that evolves from cells of origin from two distinct germ layers: MCPyV-negative MCCs from ectodermal keratinocytes and MCPyV-positive MCCs from mesodermal fibroblasts. Future epigenetic experiments may prove valuable in confirming these distinct lineages for these MCC subtypes, especially for the clinical importance the cell of origin has on MCC treatment and prevention.",
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Are there multiple cells of origin of Merkel cell carcinoma? / Sunshine, J. C.; Jahchan, N. S.; Sage, J.; Choi, Jaehyuk.

In: Oncogene, Vol. 37, No. 11, 01.03.2018, p. 1409-1416.

Research output: Contribution to journalReview article

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AB - Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology. Importantly, dramatic differences in the genetics of these two MCC subtypes suggest fundamental differences in their pathophysiology. We review these recent works and find that they provocatively suggest that MCPyV-positive and MCPyV-negative MCCs arise from two different cells of origin: The MCPyV-negative MCC from epidermal keratinocytes and the MCPyV-positive MCC from dermal fibroblasts. If true, this would represent the first cancer that we are aware of that evolves from cells of origin from two distinct germ layers: MCPyV-negative MCCs from ectodermal keratinocytes and MCPyV-positive MCCs from mesodermal fibroblasts. Future epigenetic experiments may prove valuable in confirming these distinct lineages for these MCC subtypes, especially for the clinical importance the cell of origin has on MCC treatment and prevention.

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