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Project description:Type II germ cell tumors (GCTs) are the most common neoplasia in young men of age 14-45 years. It is generally accepted that GCTs arise from a common precursor lesion, called germ cell neoplasia in situ (GCNIS), eventually developing into seminomas or non-seminomas, such as (embryonal carcinomas, ECs). The latter stem-cell like EC can further differentiate into teratomas (TE), yolk-sac tumors (YST), or choriocarcinomas (CC). Even though cisplatin-based chemotherapy is an efficacious standard of care during the management of GCT patients, the development of cisplatin resistance remains a major obstacle. As such, the surrounding tumor microenvironment and its secreted factors could endorse the development of drug resistance. These stromal cells, including immune cells (e.g. macrophages, T-lymphocytes), endothelial cells, and fibroblasts, can influence tumor cells by promoting proliferative and anti-apoptotic signaling pathways. Vice versa, microenvironmental cells can be influenced by tumor cells as well. For the identification of secreted proteins, cell lysates and supernatants from seven human germ cell tumor cell lines (seminoma: TCam-2; embryonal carcinoma (EC): 2102EP, NCCIT; choriocarcinoma (CC): JAR, JEG-3), yolk-sac tumor (YST): GCT72; 1411H) and five human cell types from the microenvironment (fibroblasts: MPAF, HVHF2; M2 macrophages: THP-1-M2; T-lymphocytes: JURKAT; endothelial cells: HUVEC) have been evaluated using liquid chromatography coupled with mass spectrometry (LC-MS).
2022-10-13 | PXD031329 | Pride
Project description:RNA-seq analysis of two Testicular Germ Cell Cancers (TGCC) of patients with chemotherapy-resistant disease. Purpose of the study was to resolve the early development and progression of the disease by whole genome sequencing, RNA-seq and methylation profiling of the primary tumor, and the targeted sequencing of purified tumor components (embryonal carcinoma (EC), teratoma (TE), and yolk sac tumor (YST), precursor lesion (Germ Cell Neoplasia In Situ (GCNIS)), and metastases. Whole genome sequencing for the two patients, T6107 and T3209, have been deposited with the European Nucleotide Archive under project accession number PRJEB20644 / study accession ERP022815 ( http://www.ebi.ac.uk/ena/data/search?query=ERP022815 ).
2019-02-11 | E-MTAB-5746 | biostudies-arrayexpress
Project description:Germ cell tumors (GCT) can be distinguished into seminoma and non-seminoma. The latter comprises embryonal carcinoma, which can further differentiate into choriocarcinoma, teratoma (TER), and yolk-sac tumors (YST). However, GCT can transform into a somatic-type malignancy (STM), eventually resulting in an unfavorable outcome. This study aimed at enlightening the molecular mechanisms leading to STM formation by comparing them to TER and YST as presumable tissues of origin, thereby paving the way for the identification of novel druggable targets.
2024-01-26 | PXD039546 | Pride
Project description:Type II germ cell tumors (GCTs) are with more than 90% the most common neoplasia in young men of age 14 - 45 years. It is generally accepted that GCTs arise from a common precursor lesion, called germ cell neoplasia in situ (GCNIS), eventually developing into seminomas or non-seminomas. The non-seminomatous stem-cell like embryonal carcinomas (EC) can further differentiate into teratomas (TE), yolk sac tumors (YST), or choriocarcinomas (CC). Orchiectomy followed by chemo- or radiotherapy is a widely used procedure in the treatment of type II GCTs, leading to high cure rates of up to 90%. Nevertheless, about 10 - 15% of patients with progressive disease relapse as a result of drug resistance and are condemned for a poor prognosis and a short survival of only a few months. Cluster of differentiation 24 (CD24) is a small, mucin-like glycosylphosphatidylinositol (GPI) anchored membrane molecule that functions both, in signal transduction and as an adhesion molecule. This glycoprotein is mainly expressed on the surface of hematopoietic, neural, muscular, and epithelial cells. Moreover, CD24 has been implicated in tumor metastasis, as fucosylated CD24 interacts with P- and E-selectin, allowing invasion of tumor cells to distal sites. High expression or amplifications of CD24 has been described in a variety of solid malignancies, such as non-small cell lung carcinoma, gliomas, breast cancer, retinoblastoma, hepatocellular carcinoma, renal cell carcinoma, cervical carcinoma, prostate cancer, urothelial carcinoma, pineal parenchymal tumors, and ovarian cancer. In this study, we investigated the putative function of CD24 and its interaction partners in (cisplatin-resistant) GCT cell lines by generating CD24-deficient EC cells by CRISPR/Cas9-mediated gene editing. Changes in the proteome between CD24-deficient cells and parental cells were measured by liquid-chromatography coupled with mass spectrometry (LS-MS).
2022-01-19 | PXD025110 | Pride
Project description:Background. MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant- GCTs, regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed ‘AAGUGC’, determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. Methods. We targeted miR-371~373 and/or miR-302/367 clusters in malignant-GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcripts inhibition, and peptide- nucleic-acid (PNA) or locked-nucleic-acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays. Results. MiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant-GCT cells, regardless of subtype (seminoma/YST/EC). Following unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with de- repression of multiple mRNAs targeted by ‘AAGUGC’ seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signaling, vesicle organization/transport, and cell-cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell-cycle effects, with increase of cells in G0/G1-phase and decrease in S-phase. Conclusion. Targeting of specific miR-371~373 and miR-302/367 microRNAs in malignant- GCTs demonstrated their functional significance, with growth inhibition mediated through cell-cycle disruption.
2024-08-01 | E-MTAB-13323 | biostudies-arrayexpress
Project description:Human germ cell tumors (GCTs) occur in infants, children, and adults, and present as germinomatous and/or non-germinomatous (embryonal carcinoma, teratoma, yolk sac tumor (YST), and choriocarcinoma) histologies at gonadal or extragonadal locations. Accurate subtyping is crucial for prognosis and treatment, but current clinical biomarkers lack sensitivity and specificity (serum proteins) or require a tissue biopsy (immunohistochemistry). Hence, less-invasive and improved subtype-specific biomarkers have potential for clinical utility. We conducted a meta-analysis of DNA methylation data (450K/EPIC array) from 15 (three original and 12 published) datasets including 713 GCTs, 109 healthy testis, and 221 healthy peripheral blood samples, revealing that GCT histology is the primary driver of methylation profiles, regardless of tumor location and patient’s age or sex. Per subtype, we identified differentially methylated regions as potential biomarkers. As proof of concept, we identified and validated two YST-specific biomarkers, i.e., APC and DPP7 promotor methylation, using methylation-sensitive restriction enzyme-based qPCR, of which DPP7 was also detectable in GCT serum-derived cell-free DNA. In conclusion, we present a novel method for in silico identification and in vitro and in vivo validation of YST subtype-specific liquid biopsy-based biomarkers. Our bioinformatic pipeline is also easily transferrable encouraging additional applications in pan(pediatric)-cancer studies beyond GCTs.
2026-03-13 | GSE303824 | GEO
Project description:Human germ cell tumors (GCTs) occur in infants, children, and adults, and present as germinomatous and/or non-germinomatous (embryonal carcinoma, teratoma, yolk sac tumor (YST), and choriocarcinoma) histologies at gonadal or extragonadal locations. Accurate subtyping is crucial for prognosis and treatment, but current clinical biomarkers lack sensitivity and specificity (serum proteins) or require a tissue biopsy (immunohistochemistry). Hence, less-invasive and improved subtype-specific biomarkers have potential for clinical utility. We conducted a meta-analysis of DNA methylation data (450K/EPIC array) from 15 (three original and 12 published) datasets including 713 GCTs, 109 healthy testis, and 221 healthy peripheral blood samples, revealing that GCT histology is the primary driver of methylation profiles, regardless of tumor location and patient’s age or sex. Per subtype, we identified differentially methylated regions as potential biomarkers. As proof of concept, we identified and validated two YST-specific biomarkers, i.e., APC and DPP7 promotor methylation, using methylation-sensitive restriction enzyme-based qPCR, of which DPP7 was also detectable in GCT serum-derived cell-free DNA. In conclusion, we present a novel method for in silico identification and in vitro and in vivo validation of YST subtype-specific liquid biopsy-based biomarkers. Our bioinformatic pipeline is also easily transferrable encouraging additional applications in pan(pediatric)-cancer studies beyond GCTs.
2026-03-13 | GSE303826 | GEO
Project description:Human germ cell tumors (GCTs) occur in infants, children, and adults, and present as germinomatous and/or non-germinomatous (embryonal carcinoma, teratoma, yolk sac tumor (YST), and choriocarcinoma) histologies at gonadal or extragonadal locations. Accurate subtyping is crucial for prognosis and treatment, but current clinical biomarkers lack sensitivity and specificity (serum proteins) or require a tissue biopsy (immunohistochemistry). Hence, less-invasive and improved subtype-specific biomarkers have potential for clinical utility. We conducted a meta-analysis of DNA methylation data (450K/EPIC array) from 15 (three original and 12 published) datasets including 713 GCTs, 109 healthy testis, and 221 healthy peripheral blood samples, revealing that GCT histology is the primary driver of methylation profiles, regardless of tumor location and patient’s age or sex. Per subtype, we identified differentially methylated regions as potential biomarkers. As proof of concept, we identified and validated two YST-specific biomarkers, i.e., APC and DPP7 promotor methylation, using methylation-sensitive restriction enzyme-based qPCR, of which DPP7 was also detectable in GCT serum-derived cell-free DNA. In conclusion, we present a novel method for in silico identification and in vitro and in vivo validation of YST subtype-specific liquid biopsy-based biomarkers. Our bioinformatic pipeline is also easily transferrable encouraging additional applications in pan(pediatric)-cancer studies beyond GCTs.
2026-03-13 | GSE303825 | GEO
Project description:Intracranial pediatric germ cell tumors (GCTs) have different histological differentiations, prognosis and clinical behaviors. Prognosis of patients with germinoma and mature teratoma is good, while patients with other types of GCTs, termed as nongerminomatous malignant germ cell tumors (NGMGCTs), require more extensive drug and irradiation treatment regimen. The mechanisms underlying different prognosis of various GCT subgroups remain elusive. We presented a distinct mRNA profile correlating with GCT histological differentiation and prognosis. 13 central nervous system GCT cases with different histological subtypes are subjected to transcriptome analysis. The histological subtypes are germinoma, mixed GCT of germinoma and mature teratoma , immature teratoma , mixed GCTs of NGMGCTs category, yolk sac tumor, immature teratoma, and embryonal carcinoma.
2010-03-09 | E-GEOD-19348 | biostudies-arrayexpress
Project description:Intracranial pediatric germ cell tumors (GCTs) have different histological differentiations, prognosis and clinical behaviors. Prognosis of patients with germinoma and mature teratoma is good, while patients with other types of GCTs, termed as nongerminomatous malignant germ cell tumors (NGMGCTs), require more extensive drug and irradiation treatment regimen. The mechanisms underlying different prognosis of various GCT subgroups remain elusive. We presented the first miRNA profile of pediatric primary intracranial GCTs. 12 central nervous system GCT cases with different histological subtypes are subjected to miRNA expression analysis. The histological subtypes are germinoma, mixed GCT of germinoma and mature teratoma , immature teratoma , mixed GCTs of NGMGCTs category, yolk sac tumor, immature teratoma, and embryonal carcinoma.
2010-05-14 | E-GEOD-19347 | biostudies-arrayexpress