Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Shintaro Fukushima
PROVIDER: E-GEOD-70787 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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: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:In plants, imprinted gene expression occurs in endosperm seed tissue and can be associated with differential DNA methylation between maternal and paternal alleles. Imprinting is theorized to have been selected for because of conflict between parental genomes in offspring, but most studies of imprinting have been conducted in Arabidopsis thaliana, an inbred primarily self-fertilizing species that should have limited parental conflict. We examined embryo and endosperm allele-specific expression and DNA methylation genome-wide in the wild outcrossing species Arabidopsis lyrata. Here we show that the majority of A. lyrata imprinted genes exhibit parentally-biased expression in A. thaliana, suggesting that there is evolutionary conservation in gene imprinting. Surprisingly, we discovered substantial interspecies differences in methylation features associated with paternally expressed imprinted genes (PEGs). Unlike A. thaliana, the maternal allele of many A. lyrata PEGs was hypermethylated in the CHG context. Increased maternal allele CHG methylation was associated with increased expression bias in favor of the paternal allele. We propose that CHG methylation maintains or reinforces repression of maternal alleles of PEGs. These data suggest that while the genes subject to imprinting are largely conserved, there is flexibility in the epigenetic mechanisms employed between closely related species to maintain monoallelic expression. This supports the idea that imprinting of specific genes is a functional phenomenon, and not simply a byproduct of seed epigenomic reprogramming. Examination of total gene expression, parent-of-origin specific allelic bias, or DNA methylation in embryo, endosperm, flower bud or seedcoat tissue from Arabidopsis lyrata accessions MN47 (MN), Karhumaki (Kar or KA), and crosses between them. High-throughput Illumina poly-A-selected mRNA-seq was used to identify imprinted genes in A. lyrata, and high-throughput Illumina whole genome bisulfite-sequencing was used to examine DNA methylation. mRNA-seq samples are designated MMxFF_T# where MM is the mother of the cross (either MN for MN47 or KA for Kar), FF is the father, T is the tissue (E for embryo, N for endosperm, S for seedcoat, b for buds), and # is the replicate numbers. Samples obtained from bisulfite sequencing follow the same naming but have suffix _BS and indicate cytosine methylation context (CpG, CHG, or CHH). For KAxMN bisulfite sequencing, additional files MMxFF_T#_BS_P_C.txt follow the same naming scheme but contain context-specific methylation data (C) from reads that mapped preferentially to one parent strain (P).
2016-09-01 | E-GEOD-76076 | biostudies-arrayexpress
Project description:Background: Germ Cell Cancers (GCC), originating from Primordial Germ Cells /gonocytes, are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS, stem cell component: embryonal carcinoma (EC)). Somatic mutations are rarely found in GCC. It has been proposed that disruption of the epigenetic constitution, either primarily or secondary (e.g. environmental influences), is involved in cancer, and specifically in GCC. Results: This study aims at identifying epigenetic footprints of SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in GCC and related disruption of germ cell maturation. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data was acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP sequencing (activating histone modifications (H3K4me3, H3K27ac)). The data show that known germ cell markers are not only present and differentiating between SE and NS at the expression level, but also in the epigenetic landscape. Conclusion: The overall similarity between TCam-2 / NCCIT supports an erased embryonic gem cell arrested in early gonadal development as common origin. Subtle difference in the (integrated) epigenetic and expression profiles indicated TCam-2 to exhibit a more germ cell like profile (enrichment Androgen regulation) while NCCIT proved more pluripotent. The results provide insight into an integrated analysis of the functional genome in GCC cell lines. Two wildtype germ cell cancer (type II germ cell tumor) cell lines were analyzed. TCam-2 (representative for the seminomatous subtype of germ cell cancer) , [1, 2]) and NCCIT (representative of the non-seminomatous (embryonal carcinoma) subtype of germ cell cancer, [3]). 1. Mizuno, Y., et al., [Establishment and characterization of a new human testicular germ cell tumor cell line (TCam-2)]. Nihon Hinyokika Gakkai Zasshi, 1993. 84(7): p. 1211-8. 2. de Jong, J., et al., Further characterization of the first seminoma cell line TCam-2. Genes Chromosomes Cancer, 2008. 47(3): p. 185-96. 3. Teshima, S., et al., Four new human germ cell tumor cell lines. Lab Invest, 1988. 59(3): p. 328-36.
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Project description:Despite extensive progress in Huntingtonâ??s Disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are highest in brain and testes, is currently unknown. To investigate the role of DNA methylation in HD pathogenesis and tissue-specific expression of HTT, we utilized the Illumina HumanMethylation450K BeadChip array to measure DNA methylation in a cohort of age-matched HD and control human cortex and liver tissues. In cortex samples, we found minimal evidence of HD-associated DNA methylation at probed sites after correction for cell heterogeneity but did observe an association to age of disease onset. By contrast, comparison of matched cortex and liver samples revealed tissue-specific DNA methylation of the HTT gene region at 38 sites (FDR < 0.05). Importantly, we identified a novel differentially methylated binding site in the HTT proximal promoter for the transcription factor CTCF. This CTCF site displayed increased occupancy in cortex, where HTT expression is higher, compared to liver. Additionally, CTCF silencing reduced the activity of a HTT promoter-reporter construct, suggesting that CTCF plays a role in regulating HTT promoter function. Overall, although we were unable to detect HD-associated DNA methylation alterations at queried sites, we found that DNA methylation may be correlated to age of disease onset in cortex tissues. Moreover, our data suggest that DNA methylation may, in part, contribute to tissue-specific HTT transcription through differential CTCF occupancy. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation measures in human cortex tissue (n = 13), with a subset of matched liver tissues (n = 5) , from a cohort of HD (n = 7) and control (n = 6) individuals in order to identify potential HD-related DNA methylation aberration in the brain as well as tissue-specific DNA methylation variation at the HTT gene locus.
2016-03-11 | E-GEOD-79064 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-04-01 | GSE70787 | 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 | 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”.
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