title: Human skin carcinoma arising from kidney transplant-derived tumor cells.
abstract: Tumor cells with donor genotype have been identified in human skin cancer after allogeneic transplantation; however, the donor contribution to the malignant epithelium has not been established. Kidney transplant recipients have an increased risk of invasive skin squamous cell carcinoma (SCC), which is associated with accumulation of the tumor suppressor p53 and TP53 mutations. In 21 skin SCCs from kidney transplant recipients, we systematically assessed p53 expression and donor/recipient origin in laser-microdissected p53+ tumor cells. In one patient, molecular analyses demonstrated that skin tumor cells had the donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft biopsy performed 7 years before the skin SCC diagnosis, we found p53+ cells in the renal tubules. We identified the same TP53 mutation in these p53+ epithelial cells from the kidney transplant. These findings provide evidence for a donor epithelial cell contribution to the malignant skin epithelium in the recipient in the setting of allogeneic kidney transplantation. This finding has theoretical implications for cancer initiation and progression and clinical implications in the context of prolonged immunosuppression and longer survival of kidney transplant patients.
authors: INSERM, U-728, Paris, France. verneuil-l@chu-caen.fr
authors: Laurence
authors: L
authors: Verneuil
authors: Mariana
authors: M
authors: Varna
authors: Philippe
authors: P
authors: Ratajczak
authors: Christophe
authors: C
authors: Leboeuf
authors: Louis-François
authors: LF
authors: Plassa
authors: Morad
authors: M
authors: Elbouchtaoui
authors: Pierre
authors: P
authors: Schneider
authors: Wissam
authors: W
authors: Sandid
authors: Celeste
authors: C
authors: Lebbé
authors: Marie-Noelle
authors: MN
authors: Peraldi
authors: François
authors: F
authors: Sigaux
authors: Hugues
authors: H
authors: de Thé
authors: Anne
authors: A
authors: Janin
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D061346:Laser Capture Microdissection; D018895:Microsatellite Repeats; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
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