Dataset Information

Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ.

ABSTRACT: Aberrant overexpression of PIWI/piRNA pathway proteins is shown for many types of tumors. Interestingly, these proteins are downregulated in testicular germ cell tumors (TGCTs) compared to normal testis tissues. Here, we used germline and TGCT markers to assess the piRNA biogenesis and function in TGCTs and their precursor germ cell neoplasia in situ (GCNIS).We used small RNA deep sequencing, qRT-PCR, and mining public RNAseq/small RNA-seq datasets to examine PIWI/piRNA gene expression and piRNA biogenesis at four stages of TGCT development: (i) germ cells in healthy testis tissues, (ii) germ cells in testis tissues adjacent to TGCTs, (iii) GCNIS cells and (iv) TGCT cells. To this end, we studied three types of samples: (a) healthy testis, (b) testis tissues adjacent to two types of TGCTs (seminomas and nonseminomas) and containing both germ cells and GCNIS cells, as well as (c) matching TGCT samples.Based on our analyses of small RNA-seq data as well as the presence/absence of expression correlation between PIWI/piRNA pathway genes and germline or TGCT markers, we can suggest that piRNA biogenesis is intact in germ cells present in healthy adult testes, and adjacent to TGCTs. Conversely, GCNIS and TGCT cells were found to lack PIWI/piRNA pathway gene expression and germline-like piRNA biogenesis. However, using an in vitro cell line model, we revealed a possible role for a short PIWIL2/HILI isoform expressed in TGCTs in posttranscriptional regulation of the youngest members of LINE and SINE classes of transposable elements. Importantly, this regulation is also implemented without involvement of germline-like biogenesis of piRNAs.Though further studies are warranted, these findings suggest that the conventional germline-like PIWI/piRNA pathway is lost in transition from germ cells to GCNIS cells.

SUBMITTER: Gainetdinov IV

PROVIDER: S-EPMC5755174 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ.

Gainetdinov Ildar V IV Skvortsova Yulia V YV Kondratieva Sofia A SA Klimov Alexey A Tryakin Alexey A AA Azhikina Tatyana L TL

BMC cancer 20180104 1

<h4>Background</h4>Aberrant overexpression of PIWI/piRNA pathway proteins is shown for many types of tumors. Interestingly, these proteins are downregulated in testicular germ cell tumors (TGCTs) compared to normal testis tissues. Here, we used germline and TGCT markers to assess the piRNA biogenesis and function in TGCTs and their precursor germ cell neoplasia in situ (GCNIS).<h4>Methods</h4>We used small RNA deep sequencing, qRT-PCR, and mining public RNAseq/small RNA-seq datasets to examine P ...[more]

PMID: 29301509

Similar Datasets

Project description:BackgroundTesticular germ cell tumors (TGCTs) account for 1-2% of all tumors in young and middle aged men. A 75-fold increase in TCGT development has been reported for monozygotic (MZ) twins. Therefore, the occurrence of simultaneous tumors in MZ twins emphasizes the importance of genetic factors that influence the risk of developing these tumors. Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development.MethodsCopy number alterations were evaluated using array-CGH (4x44K, Agilent Technologies) in one seminoma and one embryonal carcinoma (EC) from MZ twins. In addition, genomic alterations from the tumors and peripheral blood cells of the twins were compared to the parental genomes via their peripheral blood cells.ResultsEmbryonal carcinoma (Twin-1 t) presented a lower frequency of genomic alterations compared to the seminoma (Twin-2 t). One minimal common region of loss was observed in 9p13.1-p12 in the comparison between DNA from blood samples for Twin-1 and Twin-2. In this region is mapped the CNTNAP3 gene which was confirmed as involved in losses by qPCR. Comparative analysis of novel CNVs between the Twin-1 t and Twin-2 t showed five minimal common regions involving gain at chromosomes 12 (12p12.3-p11.1 and 12p13.33-p12.3), while losses were observed at 10p15.3-p15.2, 13q21.1-q21.2 and 15q11.1-q11.2. In addition, one exclusive rare copy number alteration was detected in Twin-1 t and Twin-2 t, and 19 novel alterations were identified in the Twin-2 t.ConclusionDistinct genomic profiles for MZ twins with phenotypically different TGCT were described. Of particular interest, 12p gains were detected exclusively in tumor samples. In peripheral blood samples, loss of 9p13.1-p12 was the unique novel CNV shared by the twins, confirming the involvement of CNTNAP3 gene in TGCTs development. Although similar CNV profiles were shared by both the peripheral blood and tumor samples of the twins, tumor-specific CNV loci were identified for seminoma and non-seminomatous tumors. These findings suggest the presence of de novo germline structural alterations and TGCT predisposition.

Dataset Information

Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ.

Publications

Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets