Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE70787 | GEO | 2016/04/01
SECONDARY ACCESSION(S): PRJNA289527
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-04-01 | E-GEOD-70787 | biostudies-arrayexpress
Project description:The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are “Zygotoma”.
2016-04-01 | GSE70783 | GEO
Project description:The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are “Zygotoma”.
2016-04-01 | GSE70782 | GEO
Project description:The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are âZygotomaâ. Bisulphite converted DNA from 77 samples were hybridized to the Illumina Infinium HumanMethylation450 Beadchip
2016-04-01 | E-GEOD-70783 | biostudies-arrayexpress
Project description:The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are âZygotomaâ. Genomic DNA from the 81 GCTs were hybridized to the SurePrint G3 Human CGH 8 Ã 60 K Oligo Microarrays G4450A (Agilent Technologies, Santa Clara, CA).
2016-04-01 | E-GEOD-70782 | biostudies-arrayexpress
Project description:Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma
| PRJNA289527 | ENA
Project description:The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to the gonad. Imprinted regions are erased in the gonad and later become uniparentally imprinted according to fetal sex. Here, 91 GCTs (type I-IV) and four cell lines were profiled (Illumina's HumanMethylation450BeadChip). Data was pre-processed controlling for cross hybridization, SNPs, detection rate, probe-type bias and batch effects. The annotation was extended, covering snRNAs/microRNAs, repeat elements and imprinted regions. A Hidden Markov Model-based genome segmentation was devised to identify differentially methylated genomic regions. Methylation profiles allowed for separation of clusters of non-seminomas (type II), seminomas/dysgerminomas (type II), spermatocytic seminomas (type III) and teratomas/dermoid cysts (type I/IV). The seminomas, dysgerminomas and spermatocytic seminomas were globally hypomethylated, in line with previous reports and their demethylated precursor. Differential methylation and imprinting status between subtypes reflected their presumed cell of origin. Ovarian type I teratomas and dermoid cysts showed (partial) sex specific uniparental maternal imprinting. The spermatocytic seminomas showed uniparental paternal imprinting while testicular teratomas exhibited partial imprinting erasure. Somatic imprinting in type II GCTs might indicate a cell of origin after global demethylation but before imprinting erasure. This is earlier than previously described, but agrees with the totipotent/embryonic stem cell like potential of type II GCTs and their rare extra-gonadal localization. The results support the common origin of the type I teratomas and show strong similarity between ovarian type I teratomas and dermoid cysts. In conclusion, we identified specific and global methylation differences between GCT subtypes, providing insight into their developmental timing and underlying developmental biology. Data and extended annotation are deposited at GEO (GSE58538 and GPL18809).
| S-EPMC4479500 | biostudies-literature
Project description:Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.
| S-EPMC8610002 | biostudies-literature
Project description:Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and both occurring disproportionately among young females. Additionally, MOTs and MCNs share similar clinical characteristics and immunohistochemical phenotypes. Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs sometimes arise in the context of mature cystic teratomas and other primordial germ cell (PGC) tumors. We undertook the present study to investigate whether non-teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of the gene expression profiles of MOTs [including both the mucinous borderline ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high-grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more closely related to PGCs than to either eutopic epithelial tumors or normal epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the dorsal pancreas during their descent to the gonads during early human embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data suggest a common pathway for the development of MCNs and MOTs, and suggest that these tumors may be more properly classified as germ cell tumor variants. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
| S-EPMC6240919 | biostudies-literature
Project description:Background:Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, which can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear. DNA methylation alteration is generally acknowledged to cause therapeutic resistance in cancers. We hypothesized that the pediatric NGMGCTs exhibit a different genome-wide DNA methylation pattern, which is involved in the mechanism of its therapeutic resistance. Methods:We performed methylation and hydroxymethylation DNA immunoprecipitation sequencing, mRNA expression microarray, and small RNA sequencing (smRNA-seq) to determine methylation-regulated genes, including microRNAs (miRNAs). Results:The expression levels of 97 genes and 8 miRNAs were correlated with promoter DNA methylation and hydroxymethylation status, such as the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-aza-2'-deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis showed 27 novel miRNA candidates with differential expression between germinomas and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced expression of the pro-apoptotic protein BCL2-like 11 and induces cisplatin resistance. Conclusions:We interrogated the differential DNA methylation patterns between germinomas and NGMGCTs and proposed a mechanism for chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap for further pediatric CNSGCT research and potential targets for the development of new therapeutic strategies.
| S-EPMC5909647 | biostudies-literature