Molecular Characterization of Germ Cell Tumors
Ontology highlight
ABSTRACT: We performed comprehensive molecular profiling of germ cell tumors, including whole exome sequencing and transcriptome sequencing, derived from patient samples. This project additionally explores mechanisms of chemosensivity in these patients, as well as mechanisms of tumor evolution in the context of treatment.
SECONDARY ACCESSION(S): PRJNA285373PRJNA285372
REPOSITORIES: dbGaP
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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:Characterization of the molecular changes occurring at murine meiotic initiation: identification of gene expression changes in male germ cells undergoing meiotic initiation; identification of STRA8-bound sites in mouse testes enriched for germ cells initiating meiosis
2019-02-26 | GSE115928 | GEO
Project description:Cancer-associated fibroblasts (CAF) as one abundant cell type of the tumor microenvironment are known to have tumor supporting abilities by promoting tumor proliferation and modulating the immunal landscape. In this study, germ cell tumor-derived CAF were molecular and epigenetically characterized to identify CAF secreted signal molecules which play a pivotal role in the GCT-CAF interaction.
2024-11-15 | PXD049249 | Pride
Project description:Systematic next generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to disease progression.
We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity.
| EGAS00001000958 | EGA
Project description:We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.
| S-EPMC6075738 | biostudies-literature
Project description:In the 2016 WHO classification of genitourinary tumors Muellerian tumors of the urinary tract (MTUT) comprise clear cell adenocarcinomas and endometrioid carcinomas. Since these rare tumors remained understudied, we aimed to characterize their molecular background by performing DNA- and RNA-based targeted panel sequencing. All tumors (n = 11) presented single nucleotide alterations (SNVs), with ARID1A mutations being the most prevalent (5/11, 45%). Besides frequent ARID1A mutations, loss of ARID1A protein is not a suitable marker since protein expression is (partly) preserved also in mutated cases. Copy number alterations (CNVs) were found in 64% of cases (7/11), exclusively gene amplifications. Interestingly, a functionally relevant RSPO2 gene fusion/microdeletion was discovered in the endometrioid adenocarcinoma case. Comparing our findings with mutational profiles of other tumor entities, absence of TERT promoter mutations argues for a non-urothelial origin. No similarities were also found between MTUT and kidney cancers while parallels were observed for specific SNVs with endometrial carcinomas. In conclusion, immunohistochemical PAX8-positivity and lack of TERT promoter mutations could serve as key diagnostic features in difficult cases. Thus, understanding the molecular background of these tumors helps to refine treatment options and offers the possibility of targeted therapies in cases where needed.
| S-EPMC8228991 | biostudies-literature
Project description:Adenosine to inosine (A-to-I) RNA editing occurs in a wide range of tissues and cell types and can be catalyzed by one of two adenosine deaminase acting on double stranded RNA enzymes, ADAR and ADARB1. Editing can impact both coding and non-coding regions of RNA, and in higher organisms, has been proposed to function in adaptive evolution. Neither the prevalence of A-to-I editing nor the role of either ADAR or ADARB1 has been examined in the context of germ cell development in mammals. Computational analysis of whole testis and cell type specific RNA-sequencing data followed by molecular confirmation demonstrated that A-to-I RNA editing occurs in both the germ line and in somatic Sertoli cells in two targets, Cog3 and Rpa1. Expression analysis demonstrated both Adar and Adarb1 were expressed in both Sertoli cells and in a cell-type dependent manner during germ cell development. Conditional ablation of Adar did not impact testicular RNA editing in either germ cells or Sertoli cells. Additionally, Adar ablation in either cell type did not have gross impacts on germ cell development or male fertility. In contrast, global Adarb1 knockout animals demonstrated a complete loss of A-to-I RNA editing in spite of normal germ cell development. Taken together, these observations demonstrate ADARB1 mediates A-to-I RNA editing in the testis and these editing events are dispensable for male fertility in an inbred mouse strain in the lab.
2016-12-24 | GSE92870 | GEO
Project description:microRNAs (miRNA) expression in colorectal (CR) primary tumours can facilitate a more precise molecular characterization. We identified and validated a miRNA profile associated with clinical and histopathological features that might be useful for patient stratification. In situ hybridization array using paraffin-embedded biopsies of CR primary tumours were used to screen 1436 miRNAs. 17 miRNAs were selected for validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 192) and were further correlated with clinical and histopathological data. We demonstrated that miRNAs associated to Colorectal Cancer (CRC) diagnosis age (over 50s and 60s) included miR-1-3p, miR-23b-3p, miR-27b-3p, miR-143-3p, miR-145-5p and miR-193b-5p. miR-23b-3p and miR-24-3p discriminated between Lynch Syndrome and sporadic CRC. miR-10a-5p, miR-20a-5p, miR-642b and Let-7a-5p were associated to stroma abundance. miR-642b and Let-7a-5p were associated with to peritumoral inflammation abundance. miR-1-3p, miR-143-3p and miR-145-5p correlated with mucinous component. miR-326 correlated with tumour location (right or left sided). miR-1-3p associated with tumour grade. miR-20a-5p, miR-193b-5p, miR-320a, miR-326 and miR-642b-3p associated to tumour stage and progression. Remarkably, we also demonstrated that miR-1-3p and miR-326 expression significantly associated with patient overall survival (OS). Hierarchical clustering and bioinformatics analysis indicated that selected miRNAs could re-classify the patients and work cooperatively, modulating common target genes involved in colorectal cancer key signalling pathways. In conclusion, molecular characterization of CR primary tumours based on miRNAs could lead to more accurate patient reclassification and may be useful for efficient patient management.
| S-EPMC6468580 | biostudies-literature
Project description:Molecular basis of cisplatin resistance in testicular germ cell tumors
| PRJNA562689 | ENA
Project description:Expression profiling of a panel of 101 adult male germ cell tumors and 5 normal testis specimens was performed on Affymetrix U133A and U133B microarrays. This data has been used to: 1) generate a gene classifier that predicts histology (see PMID 15870693). 2) identify candidate target genes on 12p, a region that is gained in almost 100% of germ cell tumors (see PMID 16424014) 3) identify pluripotency associated genes through comparison of pluripotent embryonal carcinoma vs. undifferentiated seminoma. ONGOING: 4) Identification of genes associated with patient outcome and cisplatin resistance. Keywords: germ cell tumor, histologic subtypes
2005-11-10 | GSE3218 | GEO