Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA388422 | ENA |
REPOSITORIES: ENA
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Project description:Testicular germ cell tumors (TGCTs) are the most common tumors in young men. Fortunately, TGCTs respond very well to cisplatin -based chemotherapy and show a low incidence of acquired resistance compared to most somatic tumors. This high sensitivity also applies to more than 80% of all TGCTs with metastatic disease. The reasons for this particularly high sensitivity of male germ cell tumors to chemotherapy seem to be multifactorial. To study this phenomenon, we have addressed the issue of whether cisplatin produces germ cell tumor specific gene expression profiles using testicular germ cell tumor derived cell lines. By means of microarray technology, we have analyzed cisplatin-induced gene expression in two well characterized human testicular germ cell tumor (TGCT) derived cell lines (833K and GCT27) which are sensitive to cisplatin treatment, and in a human colon carcinoma cell line (HCT116), to compare responses in germ cell tumor cell lines with those of tumor cells of somatic origin. We further evaluate the male germ cell tumor specificity, by mining available public databases and literature. By using SAM analysis, we identified 1794 differentially expressed genes. Among these, 1180 genes were over-expressed in TGCT cells and under-expressed in HCT116 cells and 614 genes were down-regulated in TGCT cells and up-regulated in HCT116 cells after exposure to cisplatin. Functional classification of these genes showed that they participate in a variety of different and widely distributed functional categories and biochemical pathways. Keywords: Testicular germ cell tumors (TGCT) Cisplatin, Microarray, cell type comparison, Gene expression
2007-10-01 | GSE7563 | GEO
Project description:Malignant (type II) testicular germ cell tumors (TGCT) are considered tumors of embryonic germ cell ancestry that diverge morphologically as seminoma (SE), and nonseminomas (NS), the latter including embryonal carcinoma (EC), teratoma (TE), yolk sac tumor (YS) and choriocarcinoma. We have analyzed the genomes and epigenomes of pure histological forms of TGCT (n=130) and 128 matched adjacent normal testicular tissues for TGCT core and subtype-specific DNA methylome profiles and somatic copy number aberrations (SCNA). Original data were compared with published data sets focused on differentiated and pluripotent states. First, we identified pan-TGCT recurrent erasure of maternal and paternal germline imprints and DPPA3 (STELLA), consistent with an embryonic germ cell ancestry. Beyond these conserved properties, we identified TGCT subtype-dependent epigenomic congruency with pluripotent versus somatic reference lineages, thereby establishing competency for lineage-conforming methylation reprogramming in the multi-potent common ancestor of TGCT. Notable subtype programming distinctions are as follows: the SE methylome reflects a ground-state of germ cell erasure; EC is found to harbor pervasive embryonic stem cell (ESC)-like CpH (non-CpG) methylation, absent in other TGCT and non-germ cell tumors and differentiated tissues. EC was further distinguished by ESC-like hypomethylation of NANOG, contrasting with NANOG methylation in TE, YS, and somatic tissues. Thus, EC methylomes present a novel mixed ESC/embryonic germ cell epigenomic state. TE global methylation was most convergent with somatic tissue; however, and unique among TGCT subtypes, TE manifested hypermethylation of the H19 paternal germline DMR. The YS methylome most closely resembled extra-embryonic trophoblast. The total set of findings provides evidence for a multi-potent TGCT stem cell whose progeny may harbor pluripotent, primordial germ/gonocyte, and somatic lineage-defining methylation marks. Despite such competency, no TGCT subtype restored erased parental germline imprints. TE is the exception, with H19 hypermethylation. Benign testis adjacent to TGCT exhibited a bimodal epigenotype distribution determined by spermatogenesis and significantly associated with high versus low Johnsen score. Overall, TGCT methylomes are trapped in a core embryonic germ cell-like state of DPPA3/STELLA and imprint erasure, while differential somatic and pluripotent reprogramming profiles are otherwise established.
2016-09-15 | GSE74104 | GEO
Project description:Testicular germ cells tumors (TGCTs) have a high sensitivity to cisplatin-based chemotherapy and a high cure rate, although with possible serious adverse effects. In the search for tumor suppressive drugs, the RANKL inhibitor Denosumab, used to treat osteoporosis came up as a candidate since RANKL signaling was recently identified in the testis. RANKL signals through the receptor RANK and this signaling is antagonized by the decoy receptor OPG. Here, we demonstrate expression of RANKL, RANK, and OPG in germ cell neoplasia in situ (GCNIS), TGCTs, and TGCT-derived cell lines. RANKL inhibition reduced proliferation of seminoma-derived TCam-2 cells but had no effect on embryonal carcinoma-derived NTera2 cells in vitro. Denosumab did not potentiate the effect of cisplatin treatment in vitro but inhibition of RANKL in vivo resulted in reduced tumor growth in a TCam-2 but not a NTera2 xenograft model. Moreover, Denosumab treatment decreased proliferation in human testicular GCNIS tissue culture in vitro. In TGCT patients, serum RANKL was not linked with tumor burden, relapse, or other prognostic markers. In conclusion, this study shows that the RANKL signaling system is expressed in GCNIS and seminoma where RANKL inhibition suppress tumor growth in vitro and in vivo. Future studies are needed to determine whether RANKL is important for the malignant transformation and the transition from GCNIS to invasive tumors.
2022-04-19 | GSE197389 | GEO
Project description:Several observations have pointed a link between small RNA pathway and testicular germ cell tumorigenesis. Yet, the role of small RNAs in testicular germ cell tumors (TGCTs) is still not completely understood. In this study, we characterized the expression profiles of sRNAs in 9 primary sporadic TGCTs and 2 normal testes (NTs) using a sequencing approach. Our data show comprehensive coverage of microRNAs (miRNAs) expressed in human TGCT tissues and NTs, including the identification of 29 candidate novel miRNAs. We identified the differentially expression of miR-506~514 cluster and miR-21, miR-223 in the TGCTs compared to NTs. Functionally, we showed that miR-514a-3p positively regulates apoptosis through directly regulating PEG3. We further demonstrate that PEG3 activates NF-kappa B pathway in human testicular germ cell tumors.
2015-01-16 | GSE59267 | GEO
Project description:To clarify the mechanism of cisplatin resistance in testicular germ cell tumor (TGCT), cisplatin-resistant TGCT cells (N8R and G9R) were generated from parental NEC8 cells (N8P) and TGCT patient-derived cells (TGCT-PDC)(G9P), respectively, by culture in medium containing cisplatin. We used microarrays to detail the global programme of gene expression underlying cisplatin resistance and identified up- and down-regulated genes during this process.
2022-10-17 | GSE197347 | GEO
Project description:Normal, premalignant and various histological subtypes of testicular germ cell tumor (TGCT) tissues were hybridized against Universal Human Reference RNA (Stratagene) onto Agilent 60mer oligo microarrays (GEO accession no GPL885). In vitro time series of two TGCT cell lines, NTERA2 and 2102Ep, treated with retinoic acid for 0, 3, and 7 days were also included. The data set (30 hybridizations) is particularly useful for comparisons between various histological subtypes of TGCT versus each other or versus normal testis. Keywords = 2102Ep Keywords = Agilent oligo microarrays Keywords = carcinoma in situ Keywords = choriocarcinoma Keywords = development Keywords = developmental biology Keywords = differenciation Keywords = embryogenesis Keywords = embryonal carcinoma Keywords = homo sapiens Keywords = human Keywords = human development Keywords = intratubular germ cell tumor Keywords = nonseminoma Keywords = NTera2 Keywords = pluripotency Keywords = pluripotent Keywords = retinoic acid Keywords = seminoma Keywords = teratocarcinoma Keywords = teratoma Keywords = testis Keywords = testicular germ cell tumor Keywords = testicular neoplasm Keywords = totipotency Keywords = totipotent Keywords = undifferentiated Keywords = universal human reference RNA (Stratagene) Keywords = yolk sac tumor Keywords: other
2005-07-01 | GSE1818 | GEO
Project description:Tumor-infiltrating T cells in testicular germ cell tumors (TGCT) remain poorly understood. Therefore, along with immunohistochemistry and flow cytometry, single-cell RNA sequencing (scRNA-seq) was performed on different human TGCT testes to identify immune cell composition, with particular emphasis on delineating T cell subtypes. There are various tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells that are found in other cancer entities, but their contributions to TGCT are unknown. In this study, we found that T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma. Taken together, despite significant heterogeneity between patients, this study demonstrated that T cell subtypes form a key component of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in the human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, assessing patient prognosis, and as putative targets for personalized immunotherapy.
2024-03-21 | GSE261811 | GEO
Project description:Normal, premalignant and various histological subtypes of testicular germ cell tumor (TGCT) tissues were hybridized against Universal Human Reference RNA (Stratagene) onto Agilent 60mer oligo microarrays (GEO accession no GPL885). In vitro time series of two TGCT cell lines, NTERA2 and 2102Ep, treated with retinoic acid for 0, 3, and 7 days were also included. The data set (30 hybridizations) is particularly useful for comparisons between various histological subtypes of TGCT versus each other or versus normal testis.<br><br>Data were imported from their GEO record, which contains no information about which dyes were scanned in which channels. CH1 and CH2 have therefore been used throughout.
2008-05-07 | E-GEOD-1818 | biostudies-arrayexpress
Project description:Testicular germ cell tumors and their histological subgroups
| PRJNA90499 | ENA
Project description:We used DNA content-based flow cytometry to distinguish and isolate nuclei of clonal tumor populations from primary and metastatic refractory testicular germ cell tumors (TGCTs) tissues. We then interrogated each sorted tumor populationwith whole genome aCGH and next generation sequencing (NGS). we have explored the clonal basis of refractory TGCT by investigating distinct tumor populations that were present in each tumor. Notably this included resected primary tissues and treatment refractory metastases that arose after high dose chemotherapy. These results provide new knowledge regarding the role of clonal selection and selected genomic lesions in the resistance to chemotherapy in TGCT within this exceptional cohort.
2019-02-26 | GSE123464 | GEO