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- Title
Clonogenic Cell Subpopulations Maintain Congenital Melanocytic Nevi.
- Authors
Charbel, Christelle; Fontaine, Romain H; Kadlub, Natacha; Coulomb-L'Hermine, Aurore; Rouillé, Thomas; How-Kit, Alexandre; Moguelet, Philippe; Tost, Jorg; Picard, Arnaud; Aractingi, Selim; Guégan, Sarah
- Abstract
Large congenital melanocytic nevi (lCMN) are benign melanocytic tumors associated with an increased risk of melanoma transformation. They result predominantly from a post-zygotic somatic NRAS mutation. These lesions persist and even increase after birth proportionally to the child's growth. Therefore, we asked here whether cells with clonogenic and tumorigenic properties persisted postnatally in lCMN. Subpopulations of lCMN cells expressed stem cell/progenitor lineage markers such as Sox10, Nestin, Oct4, and ABCB5. In vitro, 1 in 250 cells from fresh lCMN formed colonies that could be passaged and harbored the same NRAS mutation as the original nevus. In vivo, lCMN specimens xenografted in immunocompromised mice expanded 4-fold. BrdU+-proliferating and label-retaining melanocytes were found within the outgrowth skin tissue of these xenografts, which displayed the same benign nested architecture as the original nevus. lCMN cell suspensions were not able to expand when xenografted alone in Rag 2−/− mice. Conversely, when mixed with keratinocytes, these cells reconstituted the architecture of the human nevus with its characteristic melanocyte layout, lentiginous hyperplasia, and nested architecture. Overall, our data demonstrate that, after birth, certain lCMN cell subtypes still display features such as clonogenic potential and expand into nevus-like structures when cooperating with adjacent keratinocytes.
- Subjects
CELL populations; MELANOMA; GENETIC mutation; CANCER cell proliferation; LABORATORY mice; KERATINOCYTES; CANCER risk factors
- Publication
Journal of Investigative Dermatology, 2015, Vol 135, Issue 3, p824
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2014.437