Merkel Cell Polyomavirus‒Negative Merkel Cell Carcinoma Originating from In Situ Squamous Cell Carcinoma: A Keratinocytic Tumor with Neuroendocrine Differentiation

Thibault Kervarrec, Silke Appenzeller, Mahtab Samimi, Bhavishya Sarma, Eva Maria Sarosi, Patricia Berthon, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Astrid Blom, Nathalie Benethon, Guido Bens, Charline Nardin, Francois Aubin, Monica Dinulescu, Marie Laure Jullie, Ágnes Pekár-Lukacs, Eduardo Calonje, Soumanth Thanguturi, Anne Tallet, Marion WobserAntoine Touzé, Serge Guyétant, Roland Houben, David Schrama

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Although virus-negative Merkel cell carcinoma (MCC) is characterized by a high frequency of UV-induced mutations, the expression of two viral oncoproteins is regarded as a key mechanism driving Merkel cell polyomavirus‒positive MCC. The cells in which these molecular events initiate MCC oncogenesis have yet not been identified for both MCC subsets. A considerable proportion of virus-negative MCC is found in association with squamous cell carcinoma (SCC), suggesting (i) coincidental collision, (ii) one providing a niche for the other, or (iii) one evolving from the other. Whole-exome sequencing of four combined tumors consisting of SCC in situ and Merkel cell polyomavirus‒negative MCC showed many mutations shared between SCC and MCC in all cases, indicating a common ancestry and thereby a keratinocytic origin of these MCCs. Moreover, analyses of the combined cases as well as of pure SCC and MCC suggest that RB1 inactivation in SCC facilitates MCC development and that epigenetic changes may contribute to the SCC/MCC transition.

Originalspråkengelska
Sidor (från-till)516-527
TidskriftJournal of Investigative Dermatology
Volym142
Nummer3
Tidigt onlinedatum2021
DOI
StatusPublished - 2022

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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