Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA117771 | ENA |
REPOSITORIES: ENA
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Project description:Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these aberrations harbour one or few genes. The aim of this study is to identify recurrent focal chromosomal aberrations and their candidate driver genes in a well defined series of stage II colon cancers and assess their potential clinical relevance. High resolution DNA copy number profiles were obtained from 38 formalin fixed paraffin embedded colon cancer samples with matched normal mucosa as a reference using array comparative genomic hybridization. In total, 81 focal chromosomal aberrations were identified that harboured 177 genes. Statistical validation of focal aberrations and identification of candidate driver genes was performed by enrichment analysis and mapping copy number and mutation data of colorectal-, breast-, pancreatic cancer and glioblastomas to loci of focal aberrations in stage II colon cancer. This analysis demonstrated a significant overlap with previously identified focal amplifications in colorectal cancer, but not with cancers from other sites. In contrast, focal deletions seem less tumour type specific since they also show significant overlap with focal deletions of other sites. Focal deletions detected are significantly enriched for cancer genes and genes frequently mutated in colorectal cancer. The mRNA expression of these genes is significantly correlated with DNA copy number status, supporting the relevance of focal aberrations. Loss of 5q34 and gain of 13q22.1 were identified as independent prognostic factors of survival in this series of patients. In conclusion, focal chromosomal copy number aberrations in stage II colon cancer are enriched in cancer genes which contribute to and drive the process of colorectal cancer development. DNA copy number status of these genes correlate with mRNA expression and some are associated with clinical outcome. 38 Stage II colorectal cancer (CRC) tissue samples (FFPE) of which 19 were done on expression arrays. One sample (Stage II colorectal cancer tissue samples (FFPE) 26) was also done on the 135K NimbleGen array. Fresh frozen and FFPE of the same CRC stage I sample was done on 105K agilent. The fresh frozen was across array in silico set out against a pool of blood of 18 healthy females.
2010-04-19 | E-GEOD-17047 | biostudies-arrayexpress
Project description:Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these aberrations harbour one or few genes. The aim of this study is to identify recurrent focal chromosomal aberrations and their candidate driver genes in a well defined series of stage II colon cancers and assess their potential clinical relevance. High resolution DNA copy number profiles were obtained from 38 formalin fixed paraffin embedded colon cancer samples with matched normal mucosa as a reference using array comparative genomic hybridization. In total, 81 focal chromosomal aberrations were identified that harboured 177 genes. Statistical validation of focal aberrations and identification of candidate driver genes was performed by enrichment analysis and mapping copy number and mutation data of colorectal-, breast-, pancreatic cancer and glioblastomas to loci of focal aberrations in stage II colon cancer. This analysis demonstrated a significant overlap with previously identified focal amplifications in colorectal cancer, but not with cancers from other sites. In contrast, focal deletions seem less tumour type specific since they also show significant overlap with focal deletions of other sites. Focal deletions detected are significantly enriched for cancer genes and genes frequently mutated in colorectal cancer. The mRNA expression of these genes is significantly correlated with DNA copy number status, supporting the relevance of focal aberrations. Loss of 5q34 and gain of 13q22.1 were identified as independent prognostic factors of survival in this series of patients. In conclusion, focal chromosomal copy number aberrations in stage II colon cancer are enriched in cancer genes which contribute to and drive the process of colorectal cancer development. DNA copy number status of these genes correlate with mRNA expression and some are associated with clinical outcome.
2010-04-19 | GSE17047 | GEO
Project description:This study aims to stratify stage II and III colon cancer patients for risk of disease recurrence based on DNA aberrations, including DNA copy number aberrations (CNA) and CNA-associated chromosomal breakpoints. To this end, high quality array-CGH data of clinically well-annotated colon cancer specimens was generated using FFPE material from a selected series of primary tumor and patient-matched normal tissue.
2016-10-10 | GSE75500 | GEO
Project description:Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters for identification of high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, are established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not been investigated for this specific group of patients. The aim of the present study is to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer. Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples where hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction Results: Patients with stage II colon cancer who had relapse of disease showed significant more losses on chromosome 4, 5, 15q, 17q and 18q. When microsatellite stable (MSS) patients were analyzed separately, only losses on chromosome 4q22.1-4q35.2 predicted worse outcome in stage II colon cancer patients. No differences in clinicopathological characteristics between patients with and without relapse were observed. Conclusion: Losses on 4q22.1-4q35.2 predict worse outcome in MSS stage II colon cancer patients and may aid in the selection of patients for adjuvant therapy.
2010-07-13 | GSE17181 | GEO
Project description:Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters for identification of high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, are established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not been investigated for this specific group of patients. The aim of the present study is to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer. Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples where hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction Results: Patients with stage II colon cancer who had relapse of disease showed significant more losses on chromosome 4, 5, 15q, 17q and 18q. When microsatellite stable (MSS) patients were analyzed separately, only losses on chromosome 4q22.1-4q35.2 predicted worse outcome in stage II colon cancer patients. No differences in clinicopathological characteristics between patients with and without relapse were observed. Conclusion: Losses on 4q22.1-4q35.2 predict worse outcome in MSS stage II colon cancer patients and may aid in the selection of patients for adjuvant therapy. 40 Stage II colorectal cancer (CRC) tissue samples (FFPE), 16 with and 24 without relapse of tumor
2010-07-13 | E-GEOD-17181 | biostudies-arrayexpress
Project description:Cervical cancer results from the accumulation of (epi)genetic aberrations following persistent infection with high-risk human papillomavirus (HPV). In order to define genetic aberrations associated with cervical carcinogenesis, chromosomal profiles of high-grade cervical intraepithelial neoplasia (CIN) were generated. Common aberrations usually encompass large genomic regions and contain numerous genes, hampering identification of actual driver genes. Consequently, direct evidence of chromosomal alterations actively contributing to cervical carcinogenesis has been lacking so far. By analyzing 60 high-grade CIN with high resolution arrayCGH we identified focal chromosomal aberrations that each harbour only one or a few genes. In total 74 focal aberrations were identified encoding 305 genes. Analysis of genes located within these focal aberrations, using two independent expression microarray datasets, revealed concurrent altered expression in high-grade CIN and/or cervical carcinomas compared to normal cervical samples for 8 genes: ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2 and NCR2. Gene silencing of EYA2, located within a focal gain at 20q13, significantly reduced viability and migratory capacity of HPV16-transformed keratinocytes. Interestingly, for hsa-miR-375, located within the most frequently identified focal loss at 2q35, a direct correlation between a (focal) loss and significantly reduced expression was found. Down-regulation of hsa-miR-375 expression during cervical carcinogenesis was confirmed in a second independent series of cervical tissues. Moreover, ectopic expression of hsa-miR-375 in 2 cervical carcinoma cell lines reduced cellular viability. In conclusion, our data provide a proof of concept that chromosomal aberrations are actively contributing to HPV-induced carcinogenesis and identify EYA2 and hsa-mir-375 as oncogene and tumor suppressor gene, respectively. DNA from microdissected tissues: 60 samples total. 11 high-grade CIN, <5yr preceding hrHPV infection, 43 high-grade CIN >5yr preceding hrHPV infection, 6 CIN3 adjacent to SCC
2012-12-31 | E-GEOD-34575 | biostudies-arrayexpress
Project description:Cervical cancer results from the accumulation of (epi)genetic aberrations following persistent infection with high-risk human papillomavirus (HPV). In order to define genetic aberrations associated with cervical carcinogenesis, chromosomal profiles of high-grade cervical intraepithelial neoplasia (CIN) were generated. Common aberrations usually encompass large genomic regions and contain numerous genes, hampering identification of actual driver genes. Consequently, direct evidence of chromosomal alterations actively contributing to cervical carcinogenesis has been lacking so far. By analyzing 60 high-grade CIN with high resolution arrayCGH we identified focal chromosomal aberrations that each harbour only one or a few genes. In total 74 focal aberrations were identified encoding 305 genes. Analysis of genes located within these focal aberrations, using two independent expression microarray datasets, revealed concurrent altered expression in high-grade CIN and/or cervical carcinomas compared to normal cervical samples for 8 genes: ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2 and NCR2. Gene silencing of EYA2, located within a focal gain at 20q13, significantly reduced viability and migratory capacity of HPV16-transformed keratinocytes. Interestingly, for hsa-miR-375, located within the most frequently identified focal loss at 2q35, a direct correlation between a (focal) loss and significantly reduced expression was found. Down-regulation of hsa-miR-375 expression during cervical carcinogenesis was confirmed in a second independent series of cervical tissues. Moreover, ectopic expression of hsa-miR-375 in 2 cervical carcinoma cell lines reduced cellular viability. In conclusion, our data provide a proof of concept that chromosomal aberrations are actively contributing to HPV-induced carcinogenesis and identify EYA2 and hsa-mir-375 as oncogene and tumor suppressor gene, respectively.
2012-12-31 | GSE34575 | GEO
Project description:The landscape of somatic copy-number alterations (SCNAs) affecting long non-coding RNAs (lncRNAs) in human cancer remains largely unexplored. While the majority of lncRNAs remains to be functionally characterized, several have been implicated in cancer development and metastasis. Considering the plethora of lncRNAs genes that is currently reported, it is conceivable that several lncRNAs might function as oncogenes or tumor suppressor genes. We devised a strategy to detect focal lncRNA SCNAs using a custom DNA microarray platform probing 20 418 lncRNA genes. By screening a panel of 80 cancer cell lines, we detected numerous focal aberrations targeting one or multiple lncRNAs without affecting neighboring protein-coding genes. These focal aberrations are highly suggestive for a tumor suppressive or oncogenic role of the targeted lncRNA gene. Although functional validation remains an essential step in the further characterization of the involved candidate cancer lncRNAs, our results provide a direct way of prioritizing candidate lncRNAs involved in cancer pathogenesis.
2017-01-01 | GSE85444 | GEO
Project description:Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here, we describe a systematic method called Genomic Identification of Significant Targets in Cancer (GISTIC) designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving ~35 significant events, including 16-18 broad events near chromosome-arm size and 16-21 focal events. About half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have different properties than those with overlapping focal EGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome. Keywords: SNP analysis, gliomas, chromosomal aberrations
2007-12-11 | GSE9635 | GEO
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.
2008-08-29 | GSE12523 | GEO