DNA copy number changes in young gastric cancer patients with special reference to chromosome 19.
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ABSTRACT:
SUBMITTER: Varis A
PROVIDER: S-EPMC2741104 | biostudies-other | 2003 Jun
REPOSITORIES: biostudies-other
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Project description:BackgroundGastric cancer is common cancer. Discovering novel genetic biomarkers might help to identify high-risk individuals. Copy number variation (CNV) has recently been shown to influence risk for several cancers. The aim of the present study was sought to test the association between copy number at a variant region and GC.MethodsA total of 110 gastric cancer patients and 325 healthy volunteers were enrolled in this study. We searched for a CNV and found a CNV (Variation 7468) containing part of the APC gene, the SRP19 gene and the REEP5 gene. We chose four probes targeting at APC-intron8, APC-exon9, SRP19 and REEP5 to interrogate this CNV. Specific Taqman probes labeled by different reporter fluorophores were used in a real-time PCR platform to obtain copy number. Both the original non-integer data and transformed integer data on copy number were used for analyses.ResultsGastric caner patients had a lower non-integer copy number than controls for the APC-exon9 probe (Adjusted p?=?0.026) and SRP19 probe (Adjusted p?=?0.002). The analysis of integer copy number yielded a similar pattern although less significant (Adjusted p?=?0.07 for APC-exon9 probe and Adjusted p?=?0.02 for SRP19 probe).ConclusionsLosses of a CNV at 5q22, especially in the DNA region surrounding APC-exon 9, may be associated with a higher risk of gastric cancer.
| S-EPMC4161348 | biostudies-literature
Project description:BackgroundOverall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts.MethodsMultiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data.ResultsWe observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors.ConclusionsIn MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.
| S-EPMC4445249 | biostudies-literature
Project description:MotivationSomatic DNA copy number alterations (CNAs) arise in tumor tissue because of underlying genomic instability. Recurrent CNAs that occur in the same genomic region across multiple independent samples are of interest to researchers because they may contain genes that contribute to the cancer phenotype. However, differences in copy number states between cancers are also commonly of interest, for example when comparing tumors with distinct morphologies in the same anatomic location. Current methodologies are limited by their inability to perform direct comparisons of CNAs between tumor cohorts, and thus they cannot formally assess the statistical significance of observed copy number differences or identify regions of the genome where these differences occur.ResultsWe introduce the DiNAMIC.Duo R package that can be used to identify recurrent CNAs in a single cohort or recurrent copy number differences between two cohorts, including when neither cohort is copy neutral. The package utilizes Python scripts for computational efficiency and provides functionality for producing figures and summary output files.Availability and implementationThe DiNAMIC.Duo R package is available from CRAN at https://cran.r-project.org/web/packages/DiNAMIC.Duo/index.html. This article uses publicly available data from the Broad Institute TCGA Genome Data Analysis Center, https://doi.org/10.7908/C11G0KM9.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9477516 | biostudies-literature
Project description:Gene amplifications and deletions frequently contribute to tumorigenesis. Characterization of these DNA copy-number changes is important for both the basic understanding of cancer and its diagnosis. Comparative genomic hybridization (CGH) was developed to survey DNA copy-number variations across a whole genome. With CGH, differentially labelled test and reference genomic DNAs are co-hybridized to normal metaphase chromosomes, and fluorescence ratios along the length of chromosomes provide a cytogenetic representation of DNA copy-number variation. CGH, however, has a limited ( approximately 20 Mb) mapping resolution, and higher-resolution techniques, such as fluorescence in situ hybridization (FISH), are prohibitively labour-intensive on a genomic scale. Array-based CGH, in which fluorescence ratios at arrayed DNA elements provide a locus-by-locus measure of DNA copy-number variation, represents another means of achieving increased mapping resolution. Published array CGH methods have relied on large genomic clone (for example BAC) array targets and have covered only a small fraction of the human genome. cDNAs representing over 30,000 radiation-hybrid (RH)-mapped human genes provide an alternative and readily available genomic resource for mapping DNA copy-number changes. Although cDNA microarrays have been used extensively to characterize variation in human gene expression, human genomic DNA is a far more complex mixture than the mRNA representation of human cells. Therefore, analysis of DNA copy-number variation using cDNA microarrays would require a sensitivity of detection an order of magnitude greater than has been routinely reported. We describe here a cDNA microarray-based CGH method, and its application to DNA copy-number variation analysis in breast cancer cell lines and tumours. This study is described more fully in Pollack JR et al.(1999) Nat Genet 23:41-6 Keywords: other
2002-06-27 | GSE49 | GEO
Project description:Gene amplifications and deletions frequently contribute to tumorigenesis. Characterization of these DNA copy-number changes is important for both the basic understanding of cancer and its diagnosis. Comparative genomic hybridization (CGH) was developed to survey DNA copy-number variations across a whole genome. With CGH, differentially labelled test and reference genomic DNAs are co-hybridized to normal metaphase chromosomes, and fluorescence ratios along the length of chromosomes provide a cytogenetic representation of DNA copy-number variation. CGH, however, has a limited ( approximately 20 Mb) mapping resolution, and higher-resolution techniques, such as fluorescence in situ hybridization (FISH), are prohibitively labour-intensive on a genomic scale. Array-based CGH, in which fluorescence ratios at arrayed DNA elements provide a locus-by-locus measure of DNA copy-number variation, represents another means of achieving increased mapping resolution. Published array CGH methods have relied on large genomic clone (for example BAC) array targets and have covered only a small fraction of the human genome. cDNAs representing over 30,000 radiation-hybrid (RH)-mapped human genes provide an alternative and readily available genomic resource for mapping DNA copy-number changes. Although cDNA microarrays have been used extensively to characterize variation in human gene expression, human genomic DNA is a far more complex mixture than the mRNA representation of human cells. Therefore, analysis of DNA copy-number variation using cDNA microarrays would require a sensitivity of detection an order of magnitude greater than has been routinely reported. We describe here a cDNA microarray-based CGH method, and its application to DNA copy-number variation analysis in breast cancer cell lines and tumours. This study is described more fully in Pollack JR et al.(1999) Nat Genet 23:41-6
2002-06-27 | E-GEOD-49 | biostudies-arrayexpress
Project description:To test the hypothesis that microdeletions or microduplications below the resolution of a standard karyotype may be a significant cause of highly skewed X-inactivation (HSXI) in women without a cytogenetically detected X-chromosome anomaly.Cases were women with HSXI, defined as ?85% of cells in a blood sample with the same active allele at the HUMARA locus. The skewing in controls ranged from 50 to <75%. We performed an SNP microarray analysis using the Affymetrix 6.0 platform for 45 cases and 45 controls.Cases and controls did not differ in the frequency of X-chromosome copy number changes ?100 kb or in the frequency of copy number changes that contained genes. However, one woman with HSXI >90% in blood and left and right buccal smears had a 5.5-Mb deletion in Xp22.2p22.1. This deletion could affect the viability of male conceptions and may have led to the dysmorphology found in female carriers.HSXI in a blood sample is rarely due to X-chromosome copy number changes detectable by microarray.
| S-EPMC4315938 | biostudies-literature
Project description:Chloroplast genome copy number is very high in leaf tissue, with upwards of 10,000 or more copies of the chloroplast DNA (ctDNA) per leaf cell. This is often promoted as a major advantage for engineering the plastid genome, as it provides high gene copy number and thus is expected to result in high expression of foreign proteins from integrated genes. However, it is also known that ctDNA copy number and ctDNA integrity decrease as cells age. Quantitative PCR (qPCR) allows measurement of organelle DNA levels relative to a nuclear gene target. We have used this approach to determine changes in copy number of ctDNA relative to the nuclear genome at different ages of Arabidopsis plant growth and in organellar DNA polymerase mutants. The mutant plant lines have T-DNA insertions in genes encoding the two organelle localized DNA polymerases (PolIA and PolIB). Each of these mutant lines exhibits some delay in plant growth and development as compared to wild-type plants, with the PolIB plants having a more pronounced delay. Both mutant lines develop to maturity and produce viable seeds. Mutants for both proteins were observed to have a reduction in ctDNA and mtDNA copy number relative to wild type plants at all time points as measured by qPCR. Both DNA polymerase mutants had a fairly similar decrease in ctDNA copy number, while the PolIB mutant had a greater effect of reduction in mtDNA levels. However, despite similar decreases in genome copy number, RT-PCR analysis of PolIA mutants show that PolIB expression remains unchanged, suggesting that PolIA may not be essential to plant survival. Furthermore, genotypic analysis of plants from heterozygous parents display a strong pressure to maintain two functioning copies of PolIB. These results indicate that the two DNA polymerases are both important in ctDNA replication, and they are not fully redundant to each other, suggesting each has a specific function in plant organelles.
| S-EPMC4740508 | biostudies-literature
Project description: Not available
| S-EPMC10480144 | biostudies-literature
Project description:Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well as recurrent patterns of gains and losses of whole or large partial chromosome segments. A recent whole genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses the importance of DNA copy number alterations in this disease, in particular for genes implicated in neuritogenesis. Here we provide additional evidence for the importance of focal DNA copy number gains and losses, which are predominantly observed in MYCN amplified tumors. A focal 5 kb gain encompassing the MYCN regulated miR-17~92 cluster as sole gene was detected in a neuroblastoma cell line and further analyses of the array CGH data set demonstrated enrichment for other MYCN target genes in focal gains and amplifications. Next we applied an integrated genomics analysis to prioritize MYCN down regulated genes mediated by MYCN driven miRNAs within regions of focal heterozygous or homozygous deletion. We identified RGS5, a negative regulator of G-protein signaling implicated in vascular normalization, invasion and metastasis, targeted by a focal homozygous deletion, as a new MYCN target gene, down regulated through MYCN activated miRNAs. In addition, we expand the miR-17~92 regulatory network controlling TGFß signaling in neuroblastoma with the ring finger protein 11 encoding gene RNF11, which was previously shown to be targeted by the miR-17~92 member miR-19b. Taken together, our data indicate that focal DNA copy number imbalances in neuroblastoma (1) target genes that are implicated in MYCN signaling, possibly selected to reinforce MYCN oncogene addiction and (2) serve as a resource for identifying new molecular targets for treatment.
| S-EPMC3537730 | biostudies-literature
Project description:The CINdex Bioconductor package addresses an important area of high-throughput genomic analysis. It calculates the chromosome instability (CIN) index, a novel measurement that quantitatively characterizes genome-wide copy number alterations (CNAs) as a measure of CIN. The advantage of this package is an ability to compare CIN index values between several groups for patients (case and control groups), which is a typical use case in translational research. The differentially changed cytobands or chromosomes can then be linked to genes located in the affected genomic regions, as well as pathways. This enables in-depth systems biology-based network analysis and assessment of the impact of CNA on various biological processes or clinical outcomes. This package was successfully applied to analysis of DNA copy number data in colorectal cancer as a part of multi-omics integrative study as well as for analysis of several other cancer types. The source code, along with an end-to-end tutorial, and example data are freely available in Bioconductor at http://bioconductor.org/packages/CINdex/.
| S-EPMC5761903 | biostudies-literature