Identification of kidney transplant patients at risk for skin cancer by differentially methylated regions in t cells

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F.S. Peters, A.M.A. Peeters, P.R. Mandaviya, J. van de Wetering, M.G.H. Betjes, C.C. Baan, K. Boer

Chair(s): Prof. dr. F.J. Bemelman & prof. dr. R. Goldschmeding

Thursday 9 march 2017

10:00 - 10:12h at Hendrik Marsmanzaal

Categories: Parallel - Basaal

Parallel session: Parallelsessie IX – Basaal 2 - Biomarkers gerelateerd aan rejectie na orgaantransplantatie

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Skin cancer, specifically cutaneous squamous cell carcinoma (cSCC), is the most often occurring malignancy in patients after organ transplantation with an incidence of 100-200 times more compared to the general population. Biomarkers to predict post-transplant cSCC are unavailable. We hypothesized that epigenetic alterations in T cells, which are crucial in tumour immune surveillance, identify individuals at increased risk for cSCC after transplantation. Therefore, we studied genome-wide DNA methylation in T cells at time of transplantation and prior to the clinical onset of cSCC in kidney transplant (KTx) patients.

Pure T cells were isolated by  FACS sorting from PMBCs of KTx patients with (n=46) and without cSCC after transplantation (n=46). Patients with post-transplant cSCC were matched to patients without cSCC. Genome-wide DNA methylation was measured using Illumina’s Infinium 450K array. To find differentially methylated regions (DMRs) linear mixed modelling was applied to adjust for confounders followed by comb-p to find the regions.

The results showed 16 DMRs at time of transplantation between patients with post-transplant cSCC and those without post-transplant cSCC. The majority (11/16) of these DMRs were hypomethylated in patients with post-transplant cSCC and 13 of these 16 DMRs were located within the promoter region of a gene. After transplantation but prior to the clinical onset of cSCC, 7 DMRs were found of which the top results included an intragenic region of SERPINB9, an actively transcribed gene in T cells, and a known tumour suppressor microRNA. No overlap was found so far between the two groups.

These results support the hypothesis that differentially methylated regions have potential to serve as a predictive tool for the development of post-transplant cSCC both at time of transplantation and prior to the clinical onset of cSCC.