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

Kervarrec, Thibault ; Appenzeller, Silke ; Samimi, Mahtab ; Sarma, Bhavishya ; Sarosi, Eva Maria ; Berthon, Patricia ; Le Corre, Yannick ; Hainaut-Wierzbicka, Ewa ; Blom, Astrid and Benethon, Nathalie , et al. (2022) In Journal of Investigative Dermatology 142(3). p.516-527
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Investigative Dermatology
volume
142
issue
3
pages
516 - 527
publisher
Elsevier
external identifiers
  • scopus:85117260697
  • pmid:34480892
ISSN
0022-202X
DOI
10.1016/j.jid.2021.07.175
language
English
LU publication?
yes
id
1305f66e-6fb5-42e6-bd63-2ed185cb3cb6
date added to LUP
2021-12-23 10:06:43
date last changed
2024-04-20 18:11:35
@article{1305f66e-6fb5-42e6-bd63-2ed185cb3cb6,
  abstract     = {{<p>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.</p>}},
  author       = {{Kervarrec, Thibault and Appenzeller, Silke and Samimi, Mahtab and Sarma, Bhavishya and Sarosi, Eva Maria and Berthon, Patricia and Le Corre, Yannick and Hainaut-Wierzbicka, Ewa and Blom, Astrid and Benethon, Nathalie and Bens, Guido and Nardin, Charline and Aubin, Francois and Dinulescu, Monica and Jullie, Marie Laure and Pekár-Lukacs, Ágnes and Calonje, Eduardo and Thanguturi, Soumanth and Tallet, Anne and Wobser, Marion and Touzé, Antoine and Guyétant, Serge and Houben, Roland and Schrama, David}},
  issn         = {{0022-202X}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{516--527}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Investigative Dermatology}},
  title        = {{Merkel Cell Polyomavirus‒Negative Merkel Cell Carcinoma Originating from In Situ Squamous Cell Carcinoma : A Keratinocytic Tumor with Neuroendocrine Differentiation}},
  url          = {{http://dx.doi.org/10.1016/j.jid.2021.07.175}},
  doi          = {{10.1016/j.jid.2021.07.175}},
  volume       = {{142}},
  year         = {{2022}},
}