XIST-promoter demethylation as tissue biomarker for testicular germ cell tumors and spermatogenesis quality

João Lobo, Sandra P. Nunes, Ad J.M. Gillis, Daniela Barros-Silva, Vera Miranda-Gonçalves, Annette van den Berg, Mariana Cantante, Rita Guimarães, Rui Henrique, Carmen Jerónimo, Leendert H.J. Looijenga

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

23 Citaten (Scopus)


BACKGROUND: The event of X chromosome inactivation induced by XIST, which is physiologically observed in females, is retained in testicular germ cell tumors (TGCTs), as a result of a supernumerary X chromosome constitution. X chromosome inactivation also occurs in male germline, specifically during spermatogenesis. We aimed to analyze the promoter methylation status of XIST in a series of TGCT tissues, representative cell lines, and testicular parenchyma.

METHODS: Two independent cohorts were included, comprising a total of 413 TGCT samples, four (T)GCT cell lines, and 86 testicular parenchyma samples. The relative amount of methylated and demethylated XIST promoter fragments was assessed by quantitative methylation-specific PCR (qMSP) and more sensitive high-resolution melting (HRM) methylation analyses.

RESULTS: Seminomas showed a lower amount of methylated XIST fragments as compared to non-seminomas or normal testis (p < 0.0001), allowing for a good discrimination among these groups (area under the curve 0.83 and 0.81, respectively). Seminomas showed a significantly higher content of demethylated XIST as compared to non-seminomas. The percentage of demethylated XIST fragment in cell lines reflected their chromosomal constitution (number of extra X chromosomes). A novel and strong positive correlation between the Johnsen's score and XIST demethylation was identified (r = 0.75, p < 0.0001).

CONCLUSIONS: The X chromosome inactivation event and demethylated XIST promoter are promising biomarkers for TGCTs and for assessing spermatogenesis quality.

Originele taal-2Engels
Nummer van het tijdschrift9
StatusGepubliceerd - sep. 2019


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