Gene expression analysis of chromosomal regions with gain or loss of genetic material detected by comparative genomic hybridization

2004 ◽  
Vol 41 (4) ◽  
pp. 353-365 ◽  
Author(s):  
Bárbara Meléndez ◽  
Ramón Díaz-Uriarte ◽  
Marta Cuadros ◽  
Ángel Martínez-Ramírez ◽  
José Fernández-Piqueras ◽  
...  
Keyword(s):  
Gene Expression ◽  
Comparative Genomic Hybridization ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Genetic Material ◽  
Comparative Genomic ◽  
Genomic Hybridization

Array Comparative Genomic Hybridization: Impact in the Assessment of Plasma Cell Myeloma Genetic Profile and Prognosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4965-4965
Author(s):  
Annette Leon ◽  
Deborah Sevilla ◽  
Joseph M Marino ◽  
Kenneth D Moreno ◽  
Rev Obrera ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Plasma Cell ◽  
Array Comparative Genomic Hybridization ◽  
Genetic Material ◽  
Chromosome Complement ◽  
Comparative Genomic ◽  
Genetic Profile ◽  
Telomeric Region ◽  
Plasma Cell Myeloma ◽  
Genomic Hybridization

Abstract Abstract 4965 Identification of specific chromosomal alterations in plasma cell myeloma (PCM) is essential for the prognosis and treatment of this disease. Although cytogenetic chromosome and fluorescence in situ hybridization (FISH) analyses are techniques currently used for this purpose, incorporation of array comparative genomic hybridization (aCGH) analysis as described in this study, demonstrates the insufficient power of traditional techniques in characterizing the complex and heterogeneous genetic profile of this group of hematological malignancies. In our cohort, aCGH study of 500 diagnosed PCM patients identified clinically significant genomic alterations in 56% of cases compared to 22% and 32% by chromosome and FISH analyses, respectively. Important findings by aCGH include the presence of hyperdiploid chromosome complement (15 > 9 > 5 > 19 > 11 > 3 > 7 > 21 > 6 > 18 >14) in 35% of cases which is associated with a favorable prognosis, as well as adverse prognostic markers such as hypodiploid chromosome complement (13 > Y >14 > 22> 10 >16 >8), gain of genetic material in chromosome 1q (CKS1B, PDZK1, ANP32E) and losses in chromosomes 1p (CDKN2C, FAM46C), 6q (PRDM1), 12p (ETV6, CDKN1B), and 17p (TP53) observed in 25% of patients. Recurrent alterations identified in 9% of cases only by aCGH include extra copies of genes which could be potentially poor prognostic indicators such as IRF4 (6p25. 3, transactivates MYC oncogene), IL-6 (7p15. 3, growth factor), BRAF (7q34, regulating the MAP kinase/ERKs signaling pathway), CYLC2 (9q31. 1, active cyclin in cell cycle progression from G1 to S phase), and genes located in the telomeric region of chromosome Xq. The results obtained in this study demonstrate the superior resolution and detection rate of aCGH technology in understanding the genetic heterogeneity of PCM as well as the importance of incorporating this methodology into current algorithms for the diagnosis and prognosis of plasma cell disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Gene networks and transcriptional regulators associated with liver cancer development and progression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tatiana Meier ◽  
Max Timm ◽  
Matteo Montani ◽  
Ludwig Wilkens
Keyword(s):  
Gene Expression ◽  
Liver Cancer ◽  
Comparative Genomic Hybridization ◽  
Chromosomal Instability ◽  
Gene Networks ◽  
Transcriptional Regulators ◽  
Histological Evaluation ◽  
Comparative Genomic ◽  
Published Data ◽  
Genomic Hybridization

Abstract Background Treatment options for hepatocellular carcinoma (HCC) are limited, and overall survival is poor. Despite the high frequency of this malignoma, its basic disease mechanisms are poorly understood. Therefore, the aim of this study was to use different methodological approaches and combine the results to improve our knowledge on the development and progression of HCC. Methods Twenty-three HCC samples were characterized by histological, morphometric and cytogenetic analyses, as well as comparative genomic hybridization (aCGH) and genome-wide gene expression followed by a bioinformatic search for potential transcriptional regulators and master regulatory molecules of gene networks. Results Histological evaluation revealed low, intermediate and high-grade HCCs, and gene expression analysis split them into two main sets: GE1-HCC and GE2-HCC, with a low and high proliferation gene expression signature, respectively. Array-based comparative genomic hybridization demonstrated a high level of chromosomal instability, with recurrent chromosomal gains of 1q, 6p, 7q, 8q, 11q, 17q, 19p/q and 20q in both HCC groups and losses of 1p, 4q, 6q, 13q and 18q characteristic for GE2-HCC. Gene expression and bioinformatics analyses revealed that different genes and gene regulatory networks underlie the distinct biological features observed in GE1-HCC and GE2-HCC. Besides previously reported dysregulated genes, the current study identified new candidate genes with a putative role in liver cancer, e.g. C1orf35, PAFAH1B3, ZNF219 and others. Conclusion Analysis of our findings, in accordance with the available published data, argues in favour of the notion that the activated E2F1 signalling pathway, which can be responsible for both inappropriate cell proliferation and initial chromosomal instability, plays a pivotal role in HCC development and progression. A dedifferentiation switch that manifests in exaggerated gene expression changes might be due to turning on transcriptional co-regulators with broad impact on gene expression, e.g. POU2F1 (OCT1) and NFY, as a response to accumulating cell stress during malignant development. Our findings point towards the necessity of different approaches for the treatment of HCC forms with low and high proliferation signatures and provide new candidates for developing appropriate HCC therapies.

High Resolution Epigenomic Mapping of Myelodysplastic Syndrome Reveals a High Level of Functionally Important Methylation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2637-2637
Author(s):  
Li Zhou ◽  
Joanna Opalinska ◽  
Davendra Sohal ◽  
Simrit Parmar ◽  
Perry Pahanish ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Cpg Island ◽  
High Density ◽  
High Rate ◽  
Comparative Genomic ◽  
Differentially Methylated Genes ◽  
High Level ◽  
Very High

Abstract The myelodysplastic syndromes (MDS) are collections of heterogeneous hematologic diseases characterized by clonal hematopoietic defects. Even though gene expression studies have tried to differentiate between prognostic subgroups, there are concerns with standardization and validity of these studies. Decitabine and 5-azacytidine have shown activity in MDS, but it is unclear if hypomethylation can explain their efficacy. To address these issues we have developed a novel platform that uses a combination of gene expression analysis, high density array based comparative genomic hybridization (aCGH) and genome wide methylation analysis to perform an integrated high throughput epigenomic analysis of MDS. Using this approach, we conducted a pilot study in 5 patients with MDS. Gene expression analysis was performed using 37K oligo maskless arrays and high density aCGH was performed at 6Kb resolution using the Nimblegen platform. Whole genome methylation was analyzed by a recently described novel method ( Khulan et al, Genome Res. 2006 Aug;16(8)) that uses differential methylation specific digestion by HpaII and MspI followed by pcr amplification, two color labeling and hybridization to quantitatively determine individual promoter CpG island methylation. aCGH revealed a very high number of deletions (range 515–2722, mean 1073±937) and amplifications (range 614–1247, mean 843±254) not visualized by conventional cytogenetic analysis. These were also seen on peripheral blood mononuclear cells and correlated with those seen in the bone marrow. 22 common regions were found to amplified and 15 regions commonly deleted in 80% of the samples and contained genes involved in transcription and signaling. A custom human oligo array was used to determine methylation by calculating HpaII/MspI cut fragment intensity ratio. MDS samples demonstrated a very high level of methylation (range 70–84%). Expression was found to be significantly decreased for the genes that were methylated (p<.0001, T test) demonstrating the functional relevance of this assay. Analysis of common differentially methylated genes (when compared to normal samples) and their validation are ongoing. Micro deletions and amplifications seen on aCGH did not correlate with changes in global expression of the involved genes. Interestingly, large deletions (-7q) and large amplifications (+1p) correlated significantly with corresponding changes in gene expression when compared to the rest of the chromosome. (p<.0001, Anova) Integration of methylation data with aCGH data increased the predictive value of corresponding changes in gene expression. This result demonstrates that loss of heterozygosity coupled with the methylation of the remaining allele may result in pathogenic gene silencing in MDS. The high rate of methylation and DNA copy number alterations demonstrated in MDS in our study suggest that this integrated approach mightl be useful to define prognostic subgroups in future studies and aid in gene discovery.

Sign in / Sign up

Export Citation Format

Share Document