Study Sheds Light on Cellular Origin of Merkel Cell Carcinoma
Posted: Wednesday, December 5, 2018
A new study may improve the comprehension of the neuroendocrine gene-expression profile, which may help to clarify the cellular origin of Merkel cell carcinoma. Emil Chteinberg, PhD, of Maastricht University, the Netherlands, and colleagues, published the results of their genetic research on this type of skin cancer in the journal, Neoplasia.
The researchers analyzed 28 formalin-fixed and paraffin-embedded primary and metastatic Merkel cell carcinoma tissues, collected from the Maastricht University archives. They looked at the expression of three neuroendocrine key regulators: repressor element 1 silencing transcription factor (REST), neurogenic differentiation 1 (NeuroD1), and the Achaete-scute homolog 1 (ASCL1). Of the total 28 tissues, 23 tested positive for the Merkel cell polyomavirus and 5 tested negative for the Merkel cell polyomavirus.
All of the Merkel cell carcinomas were free of REST and were positive for NeuroD1 expression. “To the best of our knowledge, we report for the first time that NeuroD1 is expressed to 100% in [Merkel cell carcinoma] tissues and cell lines irrespective of [Merkel cell polyomavirus] status,” Dr. Chteinberg and colleagues reported. The Merkel cell polyomavirus–negative cell lines did indicate REST, whereas the negative REST and Merkel cell polyomavirus–positive Merkel cell carcinoma cells had decreased NeuroD1.
“The lack of the neuroendocrine master regulator ASCL1 in almost all tested [Merkel cell carcinomas] points to an important role of the absence of the negative regulator REST toward the [Merkel cell carcinoma] endocrine phenotype,” commented the scientists. “This is underlined by the expression of the REST-regulated microRNAs miR-9/9* in REST-negative [Merkel cell carcinoma] cell lines.”
