Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copy-number variation of MCL1 predicts overall survival of non-small-cell lung cancer in a Southern Chinese population.

ABSTRACT: BCL2L1 and MCL1 are key anti-apoptotic genes, and critical for cancer progression. The prognostic values of BCL2L1 and MCL1 copy-number variations (CNVs) in non-small-cell lung cancer (NSCLC) remain largely unknown. Somatic CNVs in BCL2L1 and MCL1 genes were tested in tumor tissues from 516 NSCLC patients in southern China; afterward, survival analyses were conducted with overall survival (OS) as outcome. Additionally, the associations between CNVs and mRNA expression levels were explored using data from 986 NSCLC patients in the Cancer Genome Atlas project. It was found that amplifications of BCL2L1 and MCL1 were associated with unfavorable OS of NSCLC, with adjusted hazards ratio of 1.62 (95% confident interval [CI] = 1.10-2.40; P = 0.015) and 1.39 (95% CI = 1.05-1.84; P = 0.020), respectively. Amplifications of MCL1, but not BCL2L1, were related with higher mRNA expression levels of corresponding gene, compared with non-amplifications (P = 0.005). Interestingly, after incorporating with MCL1 CNV status, clinical variables (age, sex, TNM stage, and surgical approach) showed an improved discriminatory ability to classify OS (area under curve increased from 72.2% to 74.1%; P = 0.042, DeLong's test). Overall, MCL1 CNV might be a prognostic biomarker for NSCLC, and additional investigations are needed to validate our findings.

SUBMITTER: Yin J

PROVIDER: S-EPMC4898974 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Copy number variation analysis of 18,000 fetuses in southern China

Project description:Chromosomal microarray analysis (CMA) in prenatal diagnosis detects copy number variations (CNVs) in many fetuses; however, the low penetrance and phenotypic diversity of CNVs complicate genetic counseling, resulting in limited understanding of intrauterine ultrasound phenotypes linked to CNVs. In a retrospective analysis of 25,000 cases at Fujian Maternal and Child Health Hospital, 18,000 pregnant women underwent SNP array testing (December 2015 to June 2023).

2024-08-14 | GSE274505 | GEO

MET gene copy number predicts worse overall survival in patients with non-small cell lung cancer (NSCLC); a systematic review and meta-analysis.

Project description:ObjectivesMET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC.MethodsTwo independent investigators applied parallel search strategies with the terms "MET AND lung cancer", "MET AND NSCLC", "MET gene copy number AND prognosis" in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery.ResultsAmong 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2?=?72%). MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR?=?1.78, 95% CI 1.22-2.60). When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23-1.94). This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97-4.90).ConclusionsHigher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific.

| S-EPMC4169409 | biostudies-literature

Chromosomal copy number heterogeneity predicts survival rates across cancers.

Project description:Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

| S-EPMC8160133 | biostudies-literature

Genome-wide copy number variation in Chinese schizophrenia trios

Project description:To reveal the risk CNVs of SZ in Chinese population, we recrited and enrolled 100 Chinese family trios with a schizophrenia affected children and both of their father and mother. SZ was diagnosed according to DSM-IV criteria by two independent psychiatrists. There gDNA we screen the genome-wide CNV using Agilent SurePrint G3 Human CGH Microarray Kit (1x1M) and Agilent sex-matched human DNA was used as reference. The CNV were called by ADM-2 statistical algorithms with a threshold of 6.0. We compared the burden of large rare CNVs and found that SZ probands carried more duplications and less deletions. Furtherly, we performed familial inheritance analysis of transmission disequilibrium and de novo CNV detection, validated several associated CNV loci with SZ susceptibility and also identify eight novel loci conferring risk of SZ

2021-10-01 | E-MTAB-8075 | biostudies-arrayexpress

Copy number variation in Han Chinese individuals with autism spectrum disorder.

Project description:BackgroundAutism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background.MethodsDNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity.ResultsOf the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism.ConclusionsOur findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations.

| S-EPMC4147384 | biostudies-literature

Identification of copy number variation using aCGH in Chinese chicken breeds

Project description:CNV plays an important role in the chicken genomic studies,it is imperative need to investigate the extent and pattern of CNVs using array comparative genomic hybridization (aCGH) in chinese chicken breeds for future studies associating phenotype to genome architecture. we describe systematic and genome-wide analysis of CNVs loci in five Chinese indigenous chicken breeds were evaluated by aCGH.

2014-10-10 | GSE49889 | GEO

Small-scale copy number variation and large-scale changes in gene expression.

Project description:The expression dynamics of interacting genes depends, in part, on the structure of regulatory networks. Genetic regulatory networks include an overrepresentation of subgraphs commonly known as network motifs. In this article, we demonstrate that gene copy number is an omnipresent parameter that can dramatically modify the dynamical function of network motifs. We consider positive feedback, bistable feedback, and toggle switch motifs and show that variation in gene copy number, on the order of a single or few copies, can lead to multiple orders of magnitude change in gene expression and, in some cases, switches in deterministic control. Further, small changes in gene copy number for a 3-gene motif with successive inhibition (the "repressilator") can lead to a qualitative switch in system behavior among oscillatory and equilibrium dynamics. In all cases, the qualitative change in expression is due to the nonlinear nature of transcriptional feedback in which duplicated motifs interact via common pools of transcription factors. We are able to implicitly determine the critical values of copy number which lead to qualitative shifts in system behavior. In some cases, we are able to solve for the sufficient condition for the existence of a bifurcation in terms of kinetic rates of transcription, translation, binding, and degradation. We discuss the relevance of our findings to ongoing efforts to link copy number variation with cell fate determination by viruses, dynamics of synthetic gene circuits, and constraints on evolutionary adaptation.

| S-EPMC2575476 | biostudies-other

Copy number variation of the Lipoprotein(a) (LPA) gene is associated with coronary artery disease in a southern Han Chinese population.

Project description:Copy number variations (CNVs), genomic duplication or deletion events occurring at larger than 1 kb scale, contribute to the complex diseases substantially. Lipoprotein(a) [Lp(a)] is a major inherited risk factor for atherosclerosis and coronary artery disease (CAD). We investigated the association between a CNV of the Lp(a) (LPA) gene and CAD. The case-control study included 271 CAD patients and 207 controls diagnosed by coronary angiography. A taqman real-time fluorescence PCR based technique was developed according to the 2 × 2(-ΔΔCt±SD) calculation method. We detected LPA CNVs with a range of 1, 2 and 3. The 1 copy number carriers had a significantly reduced risk of CAD compared with those with 2 copy number after adjusting for the confounding factors (P < 0.001, OR = 0.38, 95% CI 0.23-0.64). Further stratified analyses suggested a significant protective effect of the 1 copy number in the elderly population (P = 0.008), females (P = 0.007) as well as in populations with non-hyperlipidemia (P = 0.003), hypertension (P = 0.001), non-smoking (P < 0.001) and high Lp(a) (≥ 0.3 g/L) levels (P = 0.001). The 1 copy number of the LPA gene may be an independent protective factor of CAD in a southern Han Chinese population, particularly in females and the elderly.

| S-EPMC4238520 | biostudies-literature

Genome-wide patterns of copy number variation in the Chinese yak genome.

Project description:Copy number variation (CNV) represents an important source of genetic divergence that can produce drastic phenotypic differences and may therefore be subject to selection during domestication and environmental adaptation. To investigate the evolutionary dynamics of CNV in the yak genome, we used a read depth approach to detect CNV based on genome resequencing data from 14 wild and 65 domestic yaks and determined CNV regions related to domestication and adaptations to high-altitude.We identified 2,634 CNV regions (CNVRs) comprising a total of 153 megabases (5.7 % of the yak genome) and 3,879 overlapping annotated genes. Comparison between domestic and wild yak populations identified 121 potentially selected CNVRs, harboring genes related to neuronal development, reproduction, nutrition and energy metabolism. In addition, we found 85 CNVRs that are significantly different between domestic yak living in high- and low-altitude areas, including three genes related to hypoxia response and six related to immune defense. This analysis shows that genic CNVs may play an important role in phenotypic changes during yak domestication and adaptation to life at high-altitude.We present the first refined CNV map for yak along with comprehensive genomic analysis of yak CNV. Our results provide new insights into the genetic basis of yak domestication and adaptation to living in a high-altitude environment, as well as a valuable genetic resource that will facilitate future CNV association studies of important traits in yak and other bovid species.

| S-EPMC4875690 | biostudies-literature

Genome-Wide Copy Number Variation Analysis of Chinese Patients with Intellectual Disability

Project description:Objective: Intellectual disability (ID) is often sporadic, and its complex etiology can make clinical diagnosis difficult. The aims of this study were to detect genomic copy number variations (CNVs) in Chinese patients with ID, and to analyze the correlation between pathogenic CNVs and clinical phenotypes. Methods: After excluding cases of ID caused by chromosomal aneuploidy, metabolic dysfunction, or environmental factors, we enrolled 60 patients with moderate to severe ID. We performed karyotype and single-nucleotide polymorphism (SNP) array analyses for all patients. Finally, we analyzed the relationship between CNVs and phenotype using CNV databases and genotype-phenotype comparisons. Results: Karyotype analysis showed chromosomal terminal abnormalities in five patients and balanced translocations in two patients. Using SNP array analysis for 60 patients, we detected 87 CNVs in 45 patients, which included 16 pathogenic CNVs in 12 patients with a diagnostic yield of 20.0% (12/60). In one patient, we observed 14 regions of homozygosity > 10 Mb to 266 Mb. We detected a large deletion at 16q22.2 or 3q24q25 in each of two patients, in regions that have not previously been associated with specific syndromes. One case carried a 210-kb deletion at 1q21, including only one coding gene, LPPR4, which may be a candidate gene for the ID phenotype. Conclusions: Use of the genome-wide array screening method can improve the detection rate of CNVs, reveal chromosomal abnormalities that have not been well characterized by cytology, and provide a new way to locate genes for patients with the ID phenotype. However, interpretation of CNVs remains a major challenge, which is why we believe that publicly shared data on CNVs and phenotypes can create a rich database of information.

2019-06-15 | GSE83414 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data