title: Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation.
abstract: In animal models, tissue stem cells were proposed to exhibit an unexpected level of plasticity, although issues on cell fusions have lead to some controversies. Only transplantation experiments using genetically distinct recipients and donors can unequivocally show these changes in cell fate. We have analyzed oral squamous cell carcinomas arising in 8 long-term survivors of allogeneic bone marrow transplantation, in whom chronic graft-versus-host disease greatly favors development of squamous cell carcinomas, possibly as a consequence of lichenoid mucosal inflammation. With the use of 2 independent methods, (1) combined immunostaining and fluorescent in situ hybridization (FISH) analysis for X and Y chromosomes sequences in sex-mismatched grafts and (2) comparison of microsatellite typing of laser-microdissected tumor, donor, and recipient cells, in all tumors, we showed that 4 of these 8 epithelial tumors actually arose from the engrafted allogeneic bone marrow. Thus, donor-derived bone marrow cells, whether hematopoietic or mesenchymal, recruited to sites of chronic mucosal inflammation yielded epithelial tumors. Our observations therefore show that marrow cells in humans have a major role in epithelial cancer formation after allogeneic transplantation.
authors.affiliation: Inserm, U728, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Murata
authors.forename: Christophe
authors.initials: C
authors.lastname: Leboeuf
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Luc
authors.initials: L
authors.lastname: Legrès
authors.forename: Allison
authors.initials: A
authors.lastname: Desveaux
authors.forename: Mariana
authors.initials: M
authors.lastname: Varna
authors.forename: Philippe
authors.initials: P
authors.lastname: Ratajczak
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertheau
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009062:Mouth Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D012737:Sex Factors; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D055815:Young Adult