Microarray CGH Profiling Of Serous Ovarian Tumours Identifies Novel Copy Number Alterations Associated with Patient Survival
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Christopher Jones
PROVIDER: E-GEOD-29503 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OC). Therefore, we used microcell-mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into two epithelial OC cell lines. The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in one cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CGH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. A 35Mb deletion on chromosome 6 in two hybrids from one cell line mapped the candidate region proximal to 6q15 and distal to 6q22.2; and an approximate 10Mb candidate region spanning the centromere on chromosome 18 was identified in another two hybrids from the other cell line. These data confirm reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome18 has been reported. This suggests that these chromosomes may harbour genes that behave as tumour suppressors. The future identification of these genes may have a significant impact on the understanding and treatment of the disease and the identification of novel therapeutic targets. Four clones from chr 6 and chr 18 hybrids that were transferred by MMCT successfully were mapped by CGH microarray to identified transferred regions that induced neoplastic suppression in epithelial ovarian cancer cell lines (TOV21G and TOV112D).
2008-08-19 | E-GEOD-11872 | biostudies-arrayexpress
Project description:An ovarian cancer cell line study to identify possible trends between chromosomal aberrations depicted from CGH microarray profiling with expression profiling. CGH microarray profiles of a panel of ovarian cancer cell lines will be analysed and 10 cell lines with chromosomal aberrations of recurrent regions (with the strongest trend) will be taken forward for further expression array analysis to identify candidate genes. CGH microarray analyses will restrict the regions of aberrations with high resolution and accurracy, combined with expression array analysis to pinpoint candidate genes that will relate to the amplified and deleted regions. Identified candidates will allow the better understanding of mechanisms and specific pathways involved in ovarian cancer development. A collection of 31 cell lines in the laboratory will be used. CGH microarray profile analyses will be carried for all, a selection process will be used to separate the groups such as the subtypes of the cell line. An analysis program will be used to depict recurrent regions and 10 cell lines will be taken forward for further expression array analysis to identify candidate genes.
2010-10-08 | E-GEOD-12523 | biostudies-arrayexpress
Project description:DNA was extracted from postmenopausal ER positive patients with breast cancer and run on a 32K aCGH array. This included samples extracted from baseline tumors (timepoint A) and samples extracted from tumors after 3 months of Aromatase Inhibitor treatment (timepoint C).
2015-03-20 | E-MTAB-3426 | biostudies-arrayexpress
Project description:The effect of different diets (i.e. fish oil based vs vegetable oil based) on liver transcription profiles over the life history stages (freshwater and marine phases) of cultured Atlantic salmon (Salmo salar) were explored. Two groups of fish were raised from first feeding on different lipid containing diets; a) the standard 100% fish oil based diet, the other enriched with a blend of vegetable oils (75%) + fish oil (25%). Liver samples were taken from fish at four time points: two freshwater phase (as parr 36 weeks post hatch (wph); as pre-smolts, 52 wph) and two marine phase ( as post-smolts 55 wph; and as adult fish , 86 wph). A total of 96 cDNA microarray hybridisations - TRAITS / SGP Atlantic salmon 17k feature cDNA microarray - were performed ( 2 diets x 4 time points x 6 biological replicates x 2 -dye swap) using a comon pooled reference contol design.
2008-08-01 | E-TABM-449 | biostudies-arrayexpress
Project description:There is an increasing drive to replace fish oil (FO) in finfish aquaculture diets with vegetable oils (VO), driven by the short supply of FO derived from wild fish stocks. Little is known of the consequences for fish health after such substitution. The effect of dietary VO on hepatic gene expression was determined in Atlantic salmon (Salmo salar) byg a cDNA microarray analysis. Post-smolt farmed salmon were reared for x weeks on diets where the FO component of the feed was replaced with one of three different VOs - rapeseed (RO), soybean (SO) or linseed (LO). RNA from five fish fed on each diet was extracted. A total of 20 cDNA microarray hybridisations - TRAITS / SGP Atlantic salmon 17k feature cDNA microarray - were performed - 4 diets (three VO + FO control) x 5 individuals - using a common pooled reference control design. Data were obtained from 19 of the 20 hybridisations.
2008-10-27 | E-TABM-478 | biostudies-arrayexpress
Project description:Abstract Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation. 79 samples from breast tumors: 22 tumors from CHEK2 1100delC mutation carriers, 57 other tumors Five files attached represent segmented values, copy number calls, gain, loss and normal copy number probabilities.
2011-05-10 | E-GEOD-24698 | biostudies-arrayexpress
Project description:Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumor biology. Here we describe the genomic landscape of tumor samples of a homogeneous well-annotated series of patients with metastatic CRC of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal sub-regions are associated with progression free survival PFS (uncorrected single-test p-values < 0.005). These sub-regions are filtered for effect on mRNA expression, using an independent data set from The Cancer Genome Atlas (TCGA) which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of metastatic CRC reveals a number of DNA copy number aberrations associated with response to drug therapy. aCGH data of colorectal cancers of patients from 2 clinical trials (CAIRO, CAIRO2). 105 patients were treated with capecitabine first line (CAIRO arm A), 111 patients were treated with capecitabine and irinotecan first line (CAIRO arm B), and 133 patients were treated with capecitabine, oxaliplatin and bevacizumab (CAIRO2 arm A).
2014-11-14 | E-GEOD-36864 | biostudies-arrayexpress
Project description:Vitamin D is the strongest known natural anti-proliferative. A large number of studies in a wide spectrum of cancers, including epidemiological, in vitro and animal models, demonstrate that the active form of Vitamin D has anti-cancer benefits, affecting both progression and metastasis. Alike the role in calcium Vitamin D regulation, its anti-proliferative effect is thought to function through the Vitamin D receptor (VDR), although convincing evidence is lacking. Notwithstanding, separation of the calcemic and the anti-proliferative activity of Vitamin D analogues has been a major obstacle in developing new drugs for the treatment of cancer. The work presented attempts to unveil the molecular mechanism behind the anti-proliferative action of Vitamin D using genomic tools. For that purpose four independently developed Vitamin D sensitive/resistant MCF7 cell line pairs were collected. These unique biological replicates enabled us, both to increase the power of our study and to omit the use of Vitamin D. We deem this omission crucial since in the presence of Vitamin D only downstream genes involved in proliferation and cell cycle would be identified rather than causal resistance genes. The use of a variety of genomic techniques including expression, NMD and oligo CGH arrays reveal in the resistant cell lines the 11q13-14 as a region of DNA copy number loss and an altered expression of EGFR signaling pathway genes. Surprisingly, no genes known from calcium Vitamin D regulation were identified, nor did the VDR silencing by RNAi induce resistance to the sensitive cell lines. Keywords: comparative genomic hybridization, cell type comparision Several MCF7 breast tumor cell lines independently derived from the human breast cancer cell line, both resistant and sensitive to Vitamin D, were used. The pairs of cell lines (parental-resistant) were developed in different laboratories and using different methodologies; while some cell lines acquired resistance by long exposure to the physiological concentration of Vitamin D (100nM), others were induced to resistant by being exposed to increasing amounts of Vitamin D. A total of 4 microarray expression experiments were carried out. In all microarray experiments DNA from the Vitamin D resistant cell line was hybrizided agains DNA from the respsective sensitive/parental cell line.
2008-05-31 | E-GEOD-9887 | biostudies-arrayexpress
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2010-06-25 | E-GEOD-15166 | biostudies-arrayexpress
Project description:The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model-based algorithm, we identified 71 regional alterations that were recurrent in â?¥10% of cases. These ranged in size from ~200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q-, +7 or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the International Prognostic Index (IPI) Score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies. Array comparative genomic hybridization analysis of 106 follicular lymphoma diagnostic biopsies
2010-05-25 | E-GEOD-12393 | biostudies-arrayexpress