title: Varying proliferative and clonogenic potential in NRAS-mutated congenital melanocytic nevi according to size.
abstract: Congenital melanocytic nevi (CMN) are benign proliferations that may be associated with various consequences depending on their size. They are characterized by a specific molecular signature, namely a postzygotic somatic NRAS or BRAF mutation. We have recently reported that large CMN (lCMN), which are classically associated with an increased melanoma risk, harbour cell subpopulations with specific clonogenic and tumorigenic potential. We wished to ascertain whether cells displaying similar properties persisted postnatally in medium CMN (mCMN). Eighteen medium M1, nine large and one giant NRAS-mutated CMN were prospectively included in the study. Subpopulations of mCMN cells expressed stem cell/progenitor lineage markers such as Sox10, nestin and Oct4, as was the case in lCMN. Nevertheless, conversely to lCMN, mCMN cells with clonogenic properties were rarer. In vitro, approximatively one in 1500 cells isolated from fresh mCMN formed colonies that could be passaged. In vivo, mCMN seemed to harbour cells with less proliferative potential than the larger lesions as lCMN biopsies displayed a threefold expansion compared to mCMN when xenografted in Rag2(-/-) mice. Thus, our data revealed variations in clonogenicity and tumorigenic properties in NRAS-mutated CMN according to size.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U938, Saint-Antoine Research Center, Paris, France.|Université Pierre et Marie Curie-Paris VI, Paris, France.|Department of Dermatology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Guégan
authors.affiliation: Université René Descartes-Paris V, Paris, France.|Department of Maxillofacial and Plastic Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, Paris, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Kadlub
authors.affiliation: Université René Descartes-Paris V, Paris, France.|Department of Maxillofacial and Plastic Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Picard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U938, Saint-Antoine Research Center, Paris, France.|Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rouillé
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U938, Saint-Antoine Research Center, Paris, France.|Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Charbel
authors.affiliation: Université Pierre et Marie Curie-Paris VI, Paris, France.|Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Coulomb-L'Hermine
authors.affiliation: Laboratory for Functional Genomics, Fondation Jean Dausset - CEPH, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: How-Kit
authors.affiliation: Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U938, Saint-Antoine Research Center, Paris, France. selim.aractingi@gmail.com.|Université René Descartes-Paris V, Paris, France. selim.aractingi@gmail.com.|Department of Dermatology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France. selim.aractingi@gmail.com.
authors.forename: Selim
authors.initials: S
authors.lastname: Aractingi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U938, Saint-Antoine Research Center, Paris, France.|Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Romain H
authors.initials: RH
authors.lastname: Fontaine
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D063646:Carcinogenesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000209:etiology*; D009508:Nevus, Pigmented / Q000151:congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D015415:Biomarkers
keywords: NRAS mutation; congenital melanocytic nevus; immunocompromised mice; melanocyte; nevosphere