Characterization of the granulosa cell tumor transcriptome using RNA-seq
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Homo sapiens
SUBMITTER: Madeleine Birgersson
PROVIDER: E-MTAB-14294 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Granulosa cell tumours (GCTs) of the ovary are a unique subset of ovarian stromal tumours accounting for approximately five percent of all ovarian malignancies. Based on their pathologic characteristics and clinical features, GCTs can be further divided into two distinct subtypes: adult-GCTs and juvenile-GCTs. In this study, we investigate the use of microRNAs (miRNAs) as potential biomarkers for the diagnosis and prognostication of GCTs.
2017-07-20 | GSE70026 | 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: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: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 CNVs correlating with GCTs malignancy and clinical risk. 16 central nervous system GCT cases with different histological subtypes are subjected to genotyping and CNVs 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.
2010-06-24 | E-GEOD-19349 | 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 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
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.
2010-02-26 | GSE19348 | GEO
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:Germ cell tumors (GCT) originate from germ cells at different developmental stages (GCT type I – V) They are thought to inherit their methylation profile from (early embryonic) germ cells which undergo a characteristic epigenetic “reset” during maturation. This study aims to provide insight into the developmental timing and underlying biology of the various subtypes of GCTs and their (embryonic) cells of origin by identifying specific and global methylation differences between GCT subtypes. In total, 91 type I-IV GCTs and four cell lines were profiled using the Illumina HumanMethylation450 BeadChip (450K) platform. The data were pre-processed using a validated pipeline and analyzed using an in-house generated extension of the annotation manifest. Marked methylation differences were identified between GCT subtypes both on the global and local level (i.e. differentially methylated regions, imprinting control regions, promoters, etc). GCT subtypes indeed show major similarities to specific stages of (early) developing embryonic germ cells with regard to their methylation profile. The extended annotation manifest for the Illumina 450K platform and methylation datasets are readily available on GEO (GEO accession: GSE58538, GPL18809), providing an integrated hypothesis generating data source for future research. File S1. Differentially methylated regions between tumors classes as discussed in Table 1 of the associated publication. All figures. Please investigate using the genomic position as search term. File S2. Differentially methylated regions between GCT cell lines. DMRforPairs output. Significant results only. Please start from the html file.
2015-02-26 | GSE58538 | GEO