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Genetic Features of Virus-Positive Versus Virus-Negative Merkel Cell Carcinoma

By: Sarah Campen, PharmD
Posted: Wednesday, June 24, 2020

The aggressive skin cancer Merkel cell carcinoma is caused by either Merkel cell polyomavirus or ultraviolet-induced damage from excessive sunlight exposure. Gabriel J. Starrett, PhD, of the National Institutes of Health, Bethesda, Maryland, and colleagues have developed a sequencing platform to more accurately distinguish between virus-positive and virus-negative Merkel cell carcinoma by genetic features.

As part of the platform described in Genome Medicine, the researchers developed a method that improves the accuracy and sensitivity for virus detection by identifying Merkel cell polyomavirus integration sites and structure. “Integrating these data with clinical data revealed features that could impact patient outcome and improve our understanding of Merkel cell carcinoma risk factors,” stated the authors.

Deep sequencing was performed on 71 patients with Merkel cell carcinoma using the OncoPanel next-generation sequencing assay, which targets more than 400 cancer-associated genes. To delineate between virus-positive and virus-negative diseases, the researchers also employed genetic software programs to detect viral integration in the entire Merkel cell polyomavirus genome.

This two-pronged approach revealed “distinct integration junctions” in the tumor genome, where erroneous DNA repair likely integrated the host and viral DNA. This method allowed the researchers to identify virus-positive and virus-negative tumors, as well as recurrent somatic alterations common across Merkel cell carcinoma and alterations specific to each class of tumor. On a clinical note, a comparison of the molecular and clinical data from these patients revealed a surprising association between immunosuppression, virus-negative Merkel cell carcinoma, and significantly shortened overall survival.

“These results demonstrate the value of high-confidence virus detection for identifying molecular mechanisms of [ultraviolet] and viral oncogenesis in Merkel cell carcinoma,” concluded Dr. Starrett and colleagues.

Disclosure: The authors reported no conflicts of interest.



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