TY - JOUR
T1 - Merkel Cell Polyomavirus‒Negative Merkel Cell Carcinoma Originating from In Situ Squamous Cell Carcinoma
T2 - A Keratinocytic Tumor with Neuroendocrine Differentiation
AU - Kervarrec, Thibault
AU - Appenzeller, Silke
AU - Samimi, Mahtab
AU - Sarma, Bhavishya
AU - Sarosi, Eva Maria
AU - Berthon, Patricia
AU - Le Corre, Yannick
AU - Hainaut-Wierzbicka, Ewa
AU - Blom, Astrid
AU - Benethon, Nathalie
AU - Bens, Guido
AU - Nardin, Charline
AU - Aubin, Francois
AU - Dinulescu, Monica
AU - Jullie, Marie Laure
AU - Pekár-Lukacs, Ágnes
AU - Calonje, Eduardo
AU - Thanguturi, Soumanth
AU - Tallet, Anne
AU - Wobser, Marion
AU - Touzé, Antoine
AU - Guyétant, Serge
AU - Houben, Roland
AU - Schrama, David
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1016/j.jid.2021.07.175
DO - 10.1016/j.jid.2021.07.175
M3 - Article
C2 - 34480892
AN - SCOPUS:85117260697
SN - 1523-1747
VL - 142
SP - 516
EP - 527
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -