Homo sapiens
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PROVIDER: PRJNA272735 | ENA |
REPOSITORIES: ENA
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Project description:Genome-wide methylation analysis and gene expression profiling identifies genes silenced in non-seminoma cell lines [methylation]
| PRJNA272734 | ENA
Project description:Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. The initial lesion is believed to be the relatively benign precursor lesion (ICGNU), from which either highly chemosensitive seminomas or the more aggressive non-seminomas develop. Previous analyses of selected genes have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. However, the genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. Here genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data. This demonstrated that the seminoma cells exhibited very little aberrant DNA methylation while non-seminoma cells exhibited very high levels of DNA methylation. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested did indeed play a role in their silencing and many of these genes were also differentially expressed in primary tumours. Through this approach the genes silenced in the various GCT cell lines were identified. Conclusions: Several pluripotency-associated genes, never before implicated in this type of cancer, were identified as a major functional group of silenced genes. Silencing of these factors that normally suppress somatic differentiation might play an important role in the progression to non-seminoma formation.
2016-01-15 | GSE65027 | GEO
Project description:Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. The initial lesion is believed to be the relatively benign precursor lesion (ICGNU), from which either highly chemosensitive seminomas or the more aggressive non-seminomas develop. Previous analyses of selected genes have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. However, the genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. Here genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data. This demonstrated that the seminoma cells exhibited very little aberrant DNA methylation while non-seminoma cells exhibited very high levels of DNA methylation. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested did indeed play a role in their silencing and many of these genes were also differentially expressed in primary tumours. Through this approach the genes silenced in the various GCT cell lines were identified. Conclusions: Several pluripotency-associated genes, never before implicated in this type of cancer, were identified as a major functional group of silenced genes. Silencing of these factors that normally suppress somatic differentiation might play an important role in the progression to non-seminoma formation.
2016-01-15 | GSE65026 | GEO
Project description:Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. The initial lesion is believed to be the relatively benign precursor lesion (ICGNU), from which either highly chemosensitive seminomas or the more aggressive non-seminomas develop. Previous analyses of selected genes have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. However, the genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumoursâ biology have not yet been established. Here genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data. This demonstrated that the seminoma cells exhibited very little aberrant DNA methylation while non-seminoma cells exhibited very high levels of DNA methylation. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested did indeed play a role in their silencing and many of these genes were also differentially expressed in primary tumours. Through this approach the genes silenced in the various GCT cell lines were identified. Conclusions: Several pluripotency-associated genes, never before implicated in this type of cancer, were identified as a major functional group of silenced genes. Silencing of these factors that normally suppress somatic differentiation might play an important role in the progression to non-seminoma formation. Genomic DNA and RNA was extracted from cell lines representing four subtypes of GCT. RNA was subjected to Affymetric expression array analysis while DNA was bisulfite treated and analysed using Illumina Infinium 450K arrays. Statistical approaches were used to correlate methylation and expression for each gene.
2016-01-15 | E-GEOD-65027 | biostudies-arrayexpress
Project description:Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. The initial lesion is believed to be the relatively benign precursor lesion (ICGNU), from which either highly chemosensitive seminomas or the more aggressive non-seminomas develop. Previous analyses of selected genes have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. However, the genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumoursâ biology have not yet been established. Here genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data. This demonstrated that the seminoma cells exhibited very little aberrant DNA methylation while non-seminoma cells exhibited very high levels of DNA methylation. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested did indeed play a role in their silencing and many of these genes were also differentially expressed in primary tumours. Through this approach the genes silenced in the various GCT cell lines were identified. Conclusions: Several pluripotency-associated genes, never before implicated in this type of cancer, were identified as a major functional group of silenced genes. Silencing of these factors that normally suppress somatic differentiation might play an important role in the progression to non-seminoma formation. Genomic DNA and RNA was extracted from cell lines representing four subtypes of GCT. RNA was subjected to Affymetric expression array analysis while DNA was bisulfite treated and analysed using Illumina Infinium 450K arrays. Statistical approaches were used to correlate methylation and expression for each gene.
2016-01-15 | E-GEOD-65026 | biostudies-arrayexpress
Project description:Methylation-silenced genes in colorectal cancer cell lines
| PRJNA99441 | ENA
Project description:Using an oligonucleotide array, we undertook a genome-wide search for genes upregulated following treatment with a demethylating agent in two CRC cell lines. Promoter methylation status was determined in 12 CRC cell lines and 11 CRC tissues. After the treatment, 350 genes were upregulated 1.5 fold or more. Six genes (PAGE-5, VCX, MAEL, GAGED2, UCHL1, and GAGE7), which contained putative 5'CpG islands in their promoter regions, were confirmed to be silenced in CRC cell lines. The median level of UCHL1 gene expression in cell lines with methylation was significantly lower than that in cell lines without methylation (P = 0.032). The level of methylation of UCHL1 was significantly higher in tumors than in corresponding normal mucosae (P = 0.005). Chemical genomic screening led to the identification of a specific promoter subject to hypermethylation in CRC. These results suggest that aberrant promoter methylation is the primary mechanism of transcriptional silencing of the UCHL1 gene and that methylation of the UCHL1 gene promoter increases during the development and progression of CRC Keywords: Methylation Analysis This study explored methylation-silenced genes in colorectal cancer (CRC) cell lines. Using an oligonucleotide array, a genome-wide search for genes upregulated following treatment with a demethylating agent, 5-aza-2â??-deoxycitidine, in two CRC cell lines, DLD-1 and HT-29, was performed. Promoter methylation status of candidate genes silenced and upregulated following the treatment was determined in 12 CRC cell linesby methylation-specific PCR.
2010-06-11 | E-GEOD-7687 | 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.
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. 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