Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56454 | GEO | 2014/06/01
SECONDARY ACCESSION(S): PRJNA243361
REPOSITORIES: GEO
Similar Datasets
Project description:BackgroundOriginating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). During physiological germ cell formation/maturation, epigenetic processes guard homeostasis by regulating the accessibility of the DNA to facilitate transcription. Epigenetic deregulation through genetic and environmental parameters (i.e. genvironment) could disrupt embryonic germ cell development, resulting in delayed or blocked maturation. This potentially facilitates the formation of CIS and progression to invasive GCC. Therefore, determining the epigenetic and functional genomic landscape in GCC cell lines could provide insight into the pathophysiology and etiology of GCC and provide guidance for targeted functional experiments.ResultsThis study aims at identifying epigenetic footprints in 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 the pathophysiology and etiology of GCC. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data were acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP-sequencing (activating histone modifications (H3K4me3, H3K27ac)). Results indicate known germ cell markers not only to be differentiating between SE and NS at the expression level, but also in the epigenetic landscape.ConclusionThe overall similarity between TCam-2/NCCIT support an erased embryonic germ cell arrested in early gonadal development as common cell of origin although the exact developmental stage from which the tumor cells are derived might differ. Indeed, subtle difference in the (integrated) epigenetic and expression profiles indicate TCam-2 to exhibit a more germ cell-like profile, whereas NCCIT shows a more pluripotent phenotype. The results provide insight into the functional genome in GCC cell lines.
| S-EPMC4041891 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-01 | E-GEOD-56454 | 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.
2014-06-01 | GSE56382 | GEO
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.
2014-06-01 | E-GEOD-56382 | 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.
2014-06-01 | GSE56381 | GEO
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.
2014-06-01 | GSE56450 | GEO
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]). Of each cell line two biological replicates were included. 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.
2014-06-01 | E-GEOD-56381 | 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]). Of each cell line two biological replicates were included. Genomic positions reported are based on the GRch37/hg19 assembly. 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.
2014-06-01 | E-GEOD-56450 | biostudies-arrayexpress
Project description:Spermatogenesis is the process of generation of male reproductive cells from spermatogonial stem cells in the seminiferous epithelium of the testis. During spermatogenesis, key spermatogenic events such as stem cell self-renewal and commitment to meiosis, meiotic recombination, meiotic sex chromosome inactivation, followed by cellular and chromatin remodeling of elongating spermatids occur, leading to sperm cell production. All the mentioned events are at least partially controlled by the epigenetic modifications of DNA and histones. Additionally, during embryonal development in primordial germ cells, global epigenetic reprogramming of DNA occurs. In this review, we summarized the most important epigenetic modifications in the particular stages of germ cell development, in DNA and histone proteins, starting from primordial germ cells, during embryonal development, and ending with histone-to-protamine transition during spermiogenesis.
| S-EPMC9948345 | biostudies-literature
Project description:Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n?=?48) and SE (n?=?55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.
| S-EPMC6781582 | biostudies-literature