Homo sapiens
Ontology highlight
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PROVIDER: PRJNA134767 | ENA |
REPOSITORIES: ENA
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Project description:Objective: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy. Methods: Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in 114,000 genes. Results: Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of 128 months. Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation. Conclusion: Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value. Bisulphite converted DNA from the 20 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip
2011-05-04 | E-GEOD-25033 | biostudies-arrayexpress
Project description:Objective: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy. Methods: Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in 114,000 genes. Results: Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of 128 months. Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation. Conclusion: Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value.
2011-05-04 | GSE25033 | GEO
Project description:Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in ovarian cancer. A multi-institutional randomized clinical trial compared a regimen of a DNA methyl transferase (DNMT) inhibitor guadecitabine and carboplatin to physician’s choice chemotherapy for patients with recurrent platinum resistant ovarian cancer. Tumor biopsies or malignant ascites were collected at day 1 of cycle 1 (pre-guadecitabine) and after two cycles of treatment (post-decitabine). The goal of the current study was to analyze guadecitabine-induced DNA methylation and gene expression changes and correlate pretreatment levels with clinical outcomes. Epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450) and RNA sequencing revealed extensive methylation and gene expression changes induced by guadecitabine in ovarian tumors. Ninety-four gene promoters were significantly hypomethylated after treatment with guadecitabine and 949 genes were differentially expressed in pre vs. post-treatment tumors. Pathways associated with immune reactivation and DNA repair were significantly altered by guadecitabine treatment. Expression levels of 1155 genes involved in 25 networks on day 1 of cycle 1 correlated with progression free survival. Increased expression of selected genes (e.g. DOK2, miR193a) silenced through promoter methylation restored platinum sensitivity in ovarian cancer cells. Together, these results support that guadecitabine altered DNA methylation and expression of genes and gene networks correlate with re-sensitization to carboplatin in ovarian cancer patients.
2018-06-05 | GSE102119 | GEO
Project description:Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in ovarian cancer. A multi-institutional randomized clinical trial compared a regimen of a DNA methyl transferase (DNMT) inhibitor guadecitabine and carboplatin to physician’s choice chemotherapy for patients with recurrent platinum resistant ovarian cancer. Tumor biopsies or malignant ascites were collected at day 1 of cycle 1 (pre-guadecitabine) and after two cycles of treatment (post-decitabine). The goal of the current study was to analyze guadecitabine-induced DNA methylation and gene expression changes and correlate pretreatment levels with clinical outcomes. Epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450) and RNA sequencing revealed extensive methylation and gene expression changes induced by guadecitabine in ovarian tumors. Ninety-four gene promoters were significantly hypomethylated after treatment with guadecitabine and 949 genes were differentially expressed in pre vs. post-treatment tumors. Pathways associated with immune reactivation and DNA repair were significantly altered by guadecitabine treatment. Expression levels of 1155 genes involved in 25 networks on day 1 of cycle 1 correlated with progression free survival. Increased expression of selected genes (e.g. DOK2, miR193a) silenced through promoter methylation restored platinum sensitivity in ovarian cancer cells. Together, these results support that guadecitabine altered DNA methylation and expression of genes and gene networks correlate with re-sensitization to carboplatin in ovarian cancer patients.
2018-06-05 | GSE102118 | GEO
Project description:The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types. Expression data accompaniment to CSHL ROMA and MOMA3 human ovarian analysis. Correlation of expression to Methylation and Copy Number Variation in ovarian cancer.
2011-10-16 | E-GEOD-27943 | biostudies-arrayexpress
Project description:Introduction: Although High Grade Serous Ovarian Cancer (HGSOC) is considered a chemo-responsive disease, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival of <6 months. Validated biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of resistance. Methods: Differential DNA methylation was investigated in independent tumour sets using Illumina 27K HumanMethylation arrays and validated by bisulphite pyrosequencing. Gene expression was by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction into ovarian cancer cell lines. Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in HGSOC which recur by 6 months compared to after 12 months and/or with RECIST response (p<0.05, q<0.05). A decrease in methylation at these intragenic CpG sites was significantly correlated with decreased MSX1 gene expression. Low expression of MSX1 was associated with poor progression-free survival independent of known clinical prognostic features (p=0.014). Three mutant or wild-type TP53 expressing ovarian cancer cell lines, resistant to cisplatin, have reduced MSX1 expression compared to matched parental, platinum sensitive, lines. Re-expression of MSX1 in resistant lines led to cisplatin sensitisation, increased apoptosis, increased p21 and BAX expression. However, in two TP53-null cell lines, MSX1 failed to change cisplatin sensitivity. Conclusion: Hypomethylation of MSX1 is a biomarker of resistant HGSOC disease at presentation and identifies a novel mechanism of platinum drug resistance. Bisulphite converted DNA from the 86 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2015-11-26 | E-GEOD-75414 | biostudies-arrayexpress
Project description:To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from forty-three ovarian cancer tissues comprising eight early stage and thirty-five advanced stage tissues were performed using oligonucleotide microarrays of 18,716 genes. By non-negative matrix factorization analysis using 178 genes, which were extracted as stage-specific genes, 35 advanced-stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression-free survival (logrank test, p = 0.03). Of the 178 stage-specific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by Gene Ontology analysis or Ingenuity Pathway Analysis, 5 genes (ZEB2, CDH1, LTBP2, COL16A1 and ACTA2) were extracted as candidates for prognostic factors associated with progression-free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression-free survival was validated by real-time RT-PCR experiments of 37 independent advanced-stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced-stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E-cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced-stage cancer samples set (n = 74). These findings suggest that the expressions of epithelial-mesenchymal transition-related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced-stage serous ovarian cancer. Forty-three serous ovarian cancer samples were analyzed. Ten normal peritoneum samples were used as controls.
2009-07-19 | E-GEOD-12470 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma (IBC). DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer were generated using Illumina HumanMethylation450. Validation of methylation changes between normal and DCIS was performed in an independent dataset of 15 normal and 40 DCIS samples, and validation of a prognostic signature was performed on 583 breast cancer samples from The Cancer Genome Atlas. Using two independent datasets of normal breast tissue and DCIS revealed that DNA methylation profiles of DCIS were radically altered compared to normal breast tissue, involving almost 7000 genes (including CUL7 and ICAM2). Changes between DCIS and IBC involved around 1000 genes. In tumors, DNA methylation was associated with gene expression of almost 3000 genes (p<0.05, Bonferroni corrected) including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs (representing genes such as IRF6, TBX5, ZNF259, KCTD21, EPN3, MACF1 and CSNK1G2) was associated to survival of breast cancer patients with invasive tumors, as well as to survival of patients with DCIS and mixed lesions of DCIS and IBC. This work demonstrates that changes in the epigenome occurs early in the neoplastic progression, provide evidence for the possible utilization of DNA methylation based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis. Bisulphite converted DNA from the 285 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2014-08-08 | E-GEOD-60185 | biostudies-arrayexpress
Project description:The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types. We have developed a method to profile genome wide methylation. 7 ovarian normal samples and 44 tumor samples from other individuals were analyzed for CpG methylation. After inter array normalization, the tumor samples were taken together and the methylation compared to that of the normal samples to identify regions of the CpG islands that are significantly altered between the two datasets. Some of these regions were validated for their methylation as a proof of principle for the method. Kamalakaran S., et. al. Mol Oncol. 2011;5:77-92 (PMID: 21169070).
2011-10-16 | E-GEOD-27940 | biostudies-arrayexpress
Project description:The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types. Expression data accompaniment to CSHL ROMA and MOMA3 human ovarian analysis.
2011-10-17 | GSE27943 | GEO