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Human skin carcinoma arising from kidney transplant–derived tumor cells
Laurence Verneuil, … , Hugues de Thé, Anne Janin
Laurence Verneuil, … , Hugues de Thé, Anne Janin
Published August 27, 2013
Citation Information: J Clin Invest. 2013;123(9):3797-3801. https://doi.org/10.1172/JCI66721.
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Brief Report Article has an altmetric score of 50

Human skin carcinoma arising from kidney transplant–derived tumor cells

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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

Laurence Verneuil, Mariana Varna, Philippe Ratajczak, Christophe Leboeuf, Louis-François Plassa, Morad Elbouchtaoui, Pierre Schneider, Wissam Sandid, Celeste Lebbé, Marie-Noelle Peraldi, François Sigaux, Hugues de Thé, Anne Janin

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Figure 2

Donor kidney.

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Donor kidney.
(A) Kidney graft biopsy performed 7 years before skin SCC ...
(A) Kidney graft biopsy performed 7 years before skin SCC diagnosis. Laser microdissection was used to select p53+AE1/AE3+ cells in renal tubules. Scale bars: 5 μm. (B) TP53 sequencing identified the same base substitution in laser-microdissected p53+ epithelial cells from the kidney graft tubules as in skin SCC tumor cells. (C) Since sequencing showed an homozygous mutation in both skin SCC and kidney graft tubules, we checked this result. Polymorphic microsatellite marker IGP53, located in intron 1, showed loss of heterozygosity for this locus in recipient skin SCC and p53+ kidney graft tubule cells, but not in donor blood lymphocytes or p53– kidney graft tubule cells. (D) Kidney graft biopsy with staining for p53 as well as the renal stem/progenitor cell marker CD24. Double-stained cells were few and were located in kidney tubules (arrow), not in the glomerular area (G). Scale bars: 25 μm; 10 μm (insets, enlarged ×3).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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