Integrated Analysis of Gene Expression and Gene Copy Number for Gene Shaving Based on ICA Approach

2011 ◽  
Author(s):  
Yu-Ping Wang
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Integrated Analysis ◽  
Gene Shaving

scholarly journals Integrated Analysis of Gene Expression, CpG Island Methylation, and Gene Copy Number in Breast Cancer Cells by Deep Sequencing

PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e17490 ◽  
Author(s):  
Zhifu Sun ◽  
Yan W. Asmann ◽  
Krishna R. Kalari ◽  
Brian Bot ◽  
Jeanette E. Eckel-Passow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Deep Sequencing ◽  
Copy Number ◽  
Breast Cancer Cells ◽  
Cpg Island ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Integrated Analysis ◽  
Cpg Island Methylation

scholarly journals Insulin-like Growth Factor Receptor 1 (IGF1R) Gene Copy Number Is Associated With Survival in Operable Non–Small-Cell Lung Cancer: A Comparison Between IGF1R Fluorescent In Situ Hybridization, Protein Expression, and mRNA Expression

2010 ◽  
Vol 28 (13) ◽  
pp. 2174-2180 ◽  
Author(s):  
Rafal Dziadziuszko ◽  
Daniel T. Merrick ◽  
Samir E. Witta ◽  
Adelita D. Mendoza ◽  
Barbara Szostakiewicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Protein Expression ◽  
Squamous Cell ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Cell Versus

PurposeThe purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non–small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis.Patients and MethodsOne hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181).ResultsIGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis.ConclusionIGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.

Gene Expression Profile Analysis According to Recurrent Gene Copy Number Abnormalities Defines a Diffuse Large B-Cell Lymphoma Subgroup Characterized by 9p21 Locus Deletion, Ribosome Machinery Deregulation and Poor Prognosis. A GELA Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 803-803
Author(s):  
Fabrice Jardin ◽  
Jean-Philippe Jais ◽  
Thierry Jo Molina ◽  
Francoise Parmentier ◽  
Jean-Michel Picquenot ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Copy Number ◽  
Gene Copy Number ◽  
B Cell Lymphoma ◽  
Gene Copy ◽  
Bar Code ◽  
9P21 Locus

Abstract Genomic gains and losses play a crucial role in the development and progression of DLBCL. Some gains or losses are associated with particular morphologic or clinical manifestations and correlate with the “germinal center B-cell like” (GCB)/non-GCB phenotype, as defined by gene expression profiles (GEP). We previously developed a reliable and routinely single applicable PCR assay, which provided information regarding gain/loss of relevant genes, and prognosis in DLBCL, termed QMPSF (Multiplex PCR of Short Fluorescent Fragments). Here, we combined GEP and QMPSF approaches to delineate molecular pathways related to recurrent gene copy number abnormalities (GCNA) and assess their prognosis value in patients treated by R-CHOP. For this purpose a series of 69 newly diagnosed DLBCL, included in the 98–5 GELA trial with available tumor DNA was studied (median age = 69 years [59–79], IPI2–3: 64%; 4–5: 36%, 40 treated by R-CHOP and 29 by CHOP). A single QMPSF assay, validated by CGH array, to detect GCNA of 8 relevant genes including SIM1 (6q16), MYC (8q24), CDNK2A (9p21), RB1 (13q14), REL (2p13), BCL2 (18q21), TP53 (17p13), and CDKN1B (12p13) was performed. In addition a dedicated QMPSF assay that provides a “bar code” of the 9p21 locus containing CDKN2A (p16INK4a and p14ARF) and CDKN2B (p15INK4b) was designed. To delineate specific gene expression profile according to recurrent GCNA a subset of 52 patients were studied by both GEP (Affymetrix U133A) and QMPSF technologies. Gains of MYC, BCL2, and REL were observed in 13, 28 and 20 % respectively. DNA copy losses of TP53, CDNK2A, RB1 and SIM1 were observed in 9, 40, 6 and 17 % of cases respectively. Using supervised analysis, we delineated specific GEP according to the most frequent GCNA detected by QMPSF. Interestingly, a signature related to 9p21 locus (CDKN2A/CDKN2B) deletion was associated with an overexpression of several ribosome machinery coding genes and the involvement of distinct antiapoptotic molecular mechanisms. Subsequent genomic analysis with the dedicated assay indicated that in most of cases deletions were homozygous and abolished simultaneously p14arf and p16INK4a expression. With a median follow-up of 81 months, CDKN2A deletion, strongly correlates to a poor outcome in the entire cohort (5y OS=25% respectively vs.60% for patients in germline configuration, p=.003) and in the subgroup of patients treated by R-CHOP (5y OS=40% vs.70%, p=.04). Furthermore, prognosis impact of GCNA involving CDKN2A was validated in an independent set of 35 patients treated by R-CHOP. To conclude, combination of QMPSF and GEP may constitute a powerful approach to delineate new genomic pathways with prognosis impact in DLBCL. Notably, CDKN2A/CDKN2B loss, detected in more than one third of DLBCL patients constitutes a strong factor of chemoresistance that is not overcome by R combination. GEP indicates that this may be a consequence of an independent p14arf/p53 pathway, involving the well-established p14arf related ribosome regulation function.

scholarly journals Telomere Length and Telomerase Reverse Transcriptase Gene Copy Number in Patients with Papillary Thyroid Carcinoma

2011 ◽  
Vol 96 (11) ◽  
pp. E1876-E1880 ◽  
Author(s):  
Jaroslaw Jendrzejewski ◽  
Jerneja Tomsic ◽  
Gerard Lozanski ◽  
Jadwiga Labanowska ◽  
Huiling He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Papillary Thyroid Carcinoma ◽  
Telomere Length ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Telomerase Reverse Transcriptase ◽  
Papillary Thyroid ◽  
Quantitative Real Time Pcr ◽  
Tert Gene

Abstract Context: The family risk ratio for papillary thyroid carcinoma (PTC) is among the highest of all cancers. Collectively, familial cases (fPTC) and sporadic cases (sPTC) are not known to show molecular differences. However, one study reported that telomeres were markedly shorter and the telomerase reverse transcriptase (TERT) gene was amplified and up-regulated in germline DNA from patients with fPTC compared with sPTC. Objective: The aim of this study was to evaluate telomere length and TERT gene amplification and expression in blood samples of fPTC and sPTC patients in a genetically distinct population from the previous study. Design: In 42 fPTC and 65 sPTC patients, quantitative real-time PCR was employed to measure the relative telomere length (RTL) and TERT gene copy number and RNA level. To validate the results using alternative methods, we further studied a subset of the original cohort consisting of randomly chosen fPTC (n = 10) and sPTC (n = 14) patients and controls (n = 21) by assessing both telomere length by flow fluorescent in situ hybridization and TERT gene expression by quantitative real-time PCR. Results: RTL and TERT gene copy number did not differ between fPTC and sPTC (P = 0.957 and P = 0.998, respectively). The mean RTL and TERT gene expression were not significantly different among the groups of the validation series (P = 0.169 and P = 0.718, respectively). Conclusion: Our data show no difference between familial and sporadic PTC with respect to telomere length, TERT copy number, or expression in our cohort. Further investigations in additional cohorts of patients are desirable.

scholarly journals Integrated Analysis of Gene Copy Number, Copy Neutral LOH, and microRNA Profiles in Adult Acute Lymphoblastic Leukemia

2012 ◽  
Vol 136 (4) ◽  
pp. 246-255 ◽  
Author(s):  
S. Ninomiya ◽  
A. Tyybäkinoja ◽  
I. Borze ◽  
R. Räty ◽  
U.M. Saarinen-Pihkala ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Copy Number ◽  
Lymphoblastic Leukemia ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Integrated Analysis ◽  
Adult Acute Lymphoblastic Leukemia

scholarly journals Effects of Reduced Chloroplast Gene Copy Number on Chloroplast Gene Expression in Maize

2012 ◽  
Vol 160 (3) ◽  
pp. 1420-1431 ◽  
Author(s):  
Dylan B. Udy ◽  
Susan Belcher ◽  
Rosalind Williams-Carrier ◽  
José M. Gualberto ◽  
Alice Barkan
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Chloroplast Gene ◽  
Chloroplast Gene Expression

scholarly journals The pattern of gene copy number alteration (CNAs) in hepatocellular carcinoma: an in silico analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Arman Shahrisa ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Ansari ◽  
Zahra Mohammadi ◽  
Vinicio Carloni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
In Silico ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Gene Copy Number ◽  
In Silico Analysis ◽  
Gene Copy ◽  
Sequencing Data ◽  
Silico Analysis

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. In the absence of an ideal screening modality, HCC is usually diagnosed at an advanced stage. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. Here, we evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes. Results Our data show that the chr1q and chr8p are two hotspot regions for genomic amplifications and deletions respectively. Among the amplified genes, YY1AP1 (chr1q22) possessed the largest correlation between CNA and gene expression. Moreover, it showed a positive correlation between CNA and tumor grade. Regarding deleted genes, CHMP7 (chr8p21.3) possessed the largest correlation between CNA and gene expression. Protein products of both genes interact with other cellular proteins to carry out various functional roles. These include ASH1L, ZNF496, YY1, ZMYM4, CHMP4A, CHMP5, CHMP2A and CHMP3, some of which are well-known cancer-related genes. Conclusions Our in-silico analysis demonstrates the importance of copy number alterations in the pathology of HCC. These findings open a door for future studies that evaluate our results by performing additional experiments.

Thymidylate synthase (TS) expression as a prognostic molecular marker in stage II/III colon cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3577-3577
Author(s):  
Dirk Klingbiel ◽  
Edoardo Missiaglia ◽  
Pu Yan ◽  
Sabine Tejpar ◽  
Arnaud Roth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thymidylate Synthase ◽  
Copy Number ◽  
Cox Regression ◽  
Gene Copy Number ◽  
Tumor Grade ◽  
Gene Copy ◽  
Allelic Loss ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

3577 Background: Studies on the association between colorectal cancer (CC) outcome and thymidylate synthase expression have provided inconsistent results. In this study we attempted to resolve the issue by assessing the associations between TS expression and outcome in a population of primary CC patients (pts), who after resection were randomized to 5-FU/FA vs. FOLFIRI adjuvant therapy. Methods: Immunohistochemical staining for TS protein was successfully performed for 1211 pts in the PETACC3 trial. TS immunoreactivity was scored as high expression (≥75% positive) and low expression (<75% positive). Gene expression respectively copy number data were available for 853 respectively 306 of these samples. Twelve single nucleotide polymorphisms (SNPs) close to the TYMS gene were assessed in 923 pts. Association of variables with relapse-free (RFS) and overall survival (OS) was assessed using Cox regression models. Results: High TS expression and RNA level were strongly associated (log fold change 0.65, p<0.001). Both were significantly higher in proximal CC. As expected, both were associated with other characteristics of proximal CC: MSI, BRAF mutation, high tumor grade. RNA was significantly correlated with gene copy number, distal CC showing more frequent allelic loss. Three SNPs were associated with gene expression which was validated in data from the 1000 genomes project, but none with survival. High TS expression was more strongly associated with better OS in pts receiving FOLFIRI (HR 0.4, 95% CI 0.3–0.6, p<0.001), than 5-FU/FA (HR 0.8, 95% CI 0.5–1.1, p=0.13), with a significant interaction (p=0.05). Similar results were observed for RFS (HR 0.5, p<0.001 vs. HR 0.7, p=0.07; interaction p=0.11). TS expression is still highly prognostic in multivariate models adjusting for factors associated with risk or proximal tumors in FOLFIRI treated pts (OS: HR 0.5, p=0.008; RFS: HR 0.6, p=0.02), but not in F-FU/FA treated pts (OS and RFS: HR=1, p=1). Conclusions: TS expression is lower in distal CC, partly due to deletion of the TYMS locus. Pts with high TS expression have longer RFS and OS, notably when treated with FOLFIRI. For these pts addition of irinotecan to 5-FU/FA adjuvant chemotherapy might be considered. Clinical trial information: NCT00026273.

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