Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas

PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from stu...

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Bibliographic Details
Published in:Oncotarget 2016-04, Vol.7 (16), p.22439-22447
Main Authors: Gainetdinov, Ildar V, Kondratieva, Sofia A, Skvortsova, Yulia V, Zinovyeva, Marina V, Stukacheva, Elena A, Klimov, Alexey, Tryakin, Alexey A, Azhikina, Tatyana L
Format: Article
Language:English
Subjects:
Area Under Curve
Argonaute Proteins - genetics
Biomarkers, Tumor - genetics
Carcinoma in Situ - genetics
Carcinoma in Situ - pathology
DEAD-box RNA Helicases - genetics
Epigenesis, Genetic
Humans
Male
Precancerous Conditions - genetics
Precancerous Conditions - pathology
Research Paper
ROC Curve
Seminoma - genetics
Seminoma - pathology
Sensitivity and Specificity
Testicular Neoplasms - genetics
Testicular Neoplasms - pathology
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Summary:PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.7074