Gene expression profiling and gene copy-number changes in malignant mesothelioma cell lines

2007 ◽  
Vol 46 (10) ◽  
pp. 895-908 ◽  
Author(s):  
Claudia Zanazzi ◽  
Remko Hersmus ◽  
Imke M. Veltman ◽  
Ad J.M. Gillis ◽  
Ellen van Drunen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Expression Profiling ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Mesothelioma Cell ◽  
Copy Number Changes

Gene expression profiling of malignant mesothelioma cell lines: cDNA array study

2001 ◽  
Vol 91 (4) ◽  
pp. 492-496 ◽  
Author(s):  
Eeva Kettunen ◽  
Anna-Maria Niss�n ◽  
Tiina Ollikainen ◽  
Matti Taavitsainen ◽  
Johanna Tapper ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Expression Profiling ◽  
Cdna Array ◽  
Mesothelioma Cell

Gene expression profiling and copy number analysis to identify predictive molecular markers in breast cancer: Successful use of formalin fixed paraffin embedded tissue (FFPE)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 574-574
Author(s):  
M. Y. Iddawela ◽  
Y. Wang ◽  
R. Russell ◽  
G. Cowley ◽  
M. El-Sheemy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Treatment Response ◽  
Expression Profiling ◽  
Copy Number ◽  
Predictive Markers ◽  
Copy Number Analysis ◽  
Significant Differential Expression ◽  
Response To Chemotherapy ◽  
Copy Number Changes

574 Background: FFPE is a valuable and widely available resource for translational research which to date has been under-used due to technical limitations. Improvement in technology has enabled genome-wide analysis of FFPE samples. We have assessed gene expression and copy number changes in the same cohort of breast cancers to identify markers or pathways important in prediction of treatment response. Methods: FFPE tissues from patients treated with neoadjuvant adriamycin/cyclophosphamide followed by taxanes in a clinical study were used. Gene expression profiling was assessed using the cDNA mediated annealing selection and ligation assay using the cancer panel which assess 502 genes (DASL assay, Illumina). Data was analysed using BeadStudio software. Copy number changes were assessed using the Molecular inversion probe assay with the 50K SNP panel (Affymetrix, California) and analysed using Nexus software (Biodiscovery). Results: Gene expression profiling was carried out on 44 samples. 12/44 (27%) patients had a pathological complete response (pCR) following chemotherapy. Significant differential expression of genes between pCR and non-pCR cancers were shown. TNFRSF5, CTSD, BCL3, ARNT, BIRC3, TGFBR1, MLLT6, and EVI2A were over-expressed and COL18A1, FGF12, IGFBP1 and NOTCH4 which were down-regulated in cancers that have a pCR (p ≤ 0.01). Copy number changes were assessed in 33 samples and comparison of copy number changes in pCR vs. non-pCR showed gains in regions 6q22, 21q21, 4p14, 4q21, 4p14, and loss at 11q11 (p ≤ 0.01). Three regions containing microRNA coding sequences, mir130a (11q11) mir142 (17q23) and mir21 (17q23) showed significant loss among pCR tumours (p < 0.05). Conclusions: This feasibility study shows that FFPE can be used for gene expression and copy number analysis which is a useful tool for the discovery of predictive markers for treatment response in neoadjuvant treatment trials. The role of TNFRSF5, microRNA 21/130a/142, and 11q11 loss should be further investigated as predictive markers of response to chemotherapy. [Table: see text]

The potential role of IGF1r in young adult patients with gastroinetstinal stromal tumor (GIST)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10562-10562
Author(s):  
M. Pantaleo ◽  
A. Astolfi ◽  
M. Di Battista ◽  
P. Paterini ◽  
D. Santini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Young Adult ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Copy Number ◽  
Adult Patients ◽  
The Other ◽  
Gene Copy ◽  
Gastric Gist ◽  
Array Analysis

10562 Background: The insulin-like growth factor 1 receptor (IGF1r) is a tyrosine kinase receptor that plays a key role in the growth of normal tissues. The aberration of IGF system has been found in many cancers. Some interesting results about IGF1r were published on GISTs. However, until now the real role on the pathogenesis of this disease and its clinical implications still needs to be defined. Methods: We studied IGF1r in 8 patients affected by gastric GIST. Seven patients underwent surgery at diagnosis, whereas one patient was operated after imatinib and sunitinib treatment. Two patients were young (< 30 years old), and other patients ranged between 54 and 85 years. IGF1r was studied as gene expression profiling performed with Affymetrix GeneChip HG-U133 Plus 2.0 arrays, as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and with western blotting (WB) usinganti-IGF-IRβ (Santa Cruz Biotechnology). Results: The unsupervised analysis of gene expression profiling of our patients merged with a data set from a gastric GIST identified two groups with different regulation of IGF1r (FDR threshold to 0.2%). In particular, IGF1r was up-regulated in the two youngest patients (28 and 30 years-old). The SNPs array analysis gene copy number showed that none of the patients bore IGF1r amplification. The quantitative analysis of protein level by WB again showed that only the two youngest patients had an over-expression of IGF1r. In all the other patients the WB analysis was negative. Conclusions: These results suggest that IGF1r seems to be a novel signalling pathway other than KIT and PDGFRA in a subset of GISTs. The young adult patients had a strongly different molecular background in comparison to the other older ones. The correlation between IGF1r and mutational status of KIT and PDGFRA, clinical outcome, treatments responsiveness as well as its role as potential target deserves to be further investigated. No significant financial relationships to disclose.

scholarly journals Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans

2003 ◽  
Vol 163 (6) ◽  
pp. 2383-2395 ◽  
Author(s):  
Sabine C. Linn ◽  
Rob B. West ◽  
Jonathan R. Pollack ◽  
Shirley Zhu ◽  
Tina Hernandez-Boussard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Expression Patterns ◽  
Gene Copy Number ◽  
Dermatofibrosarcoma Protuberans ◽  
Gene Copy ◽  
Gene Expression Patterns ◽  
Copy Number Changes

scholarly journals Rearrangements of Human Mitochondrial DNA (mtDNA): New Insights into the Regulation of mtDNA Copy Number and Gene Expression

2000 ◽  
Vol 11 (4) ◽  
pp. 1471-1485 ◽  
Author(s):  
Yingying Tang ◽  
Eric A. Schon ◽  
Ekkehard Wilichowski ◽  
Martel E. Vazquez-Memije ◽  
Edgar Davidson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Cell Lines ◽  
Respiratory Chain ◽  
Copy Number ◽  
Large Scale ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Mtdna Copy Number ◽  
Human Mitochondrial Dna

Mitochondria from patients with Kearns–Sayre syndrome harboring large-scale rearrangements of human mitochondrial DNA (mtDNA; both partial deletions and a partial duplication) were introduced into human cells lacking endogenous mtDNA. Cytoplasmic hybrids containing 100% wild-type mtDNA, 100% mtDNA with partial duplications, and 100% mtDNA with partial deletions were isolated and characterized. The cell lines with 100% deleted mtDNAs exhibited a complete impairment of respiratory chain function and oxidative phosphorylation. In contrast, there were no detectable respiratory chain or protein synthesis defects in the cell lines with 100% duplicated mtDNAs. Unexpectedly, the mass of mtDNA was identical in all cell lines, despite the fact that different lines contained mtDNAs of vastly different sizes and with different numbers of replication origins, suggesting that mtDNA copy number may be regulated by tightly controlled mitochondrial dNTP pools. In addition, quantitation of mtDNA-encoded RNAs and polypeptides in these lines provided evidence that mtDNA gene copy number affects gene expression, which, in turn, is regulated at both the post-transcriptional and translational levels.

Mechanisms of Bcl-2 Protein Expression in Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 26-26
Author(s):  
Pedro Farinha ◽  
Gwyn Bebb ◽  
Reiner Siebert ◽  
Doug Horsman ◽  
Joseph M. Connors ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Expression Profiling ◽  
Copy Number ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
Gene Copy ◽  
Cell Of Origin ◽  
Bcl2 Protein ◽  
Bcl2 Gene

Abstract Background: Bcl-2 protein expression is an important biomarker in DLBCL. Gene expression profiling also has prognostic relevance in DLBCL, establishing cell-of-origin (GCB vs non-GCB) as an important predictor of survival. Using tissue microarrays (TMA), immunohistochemical staining can be used to provide biomarker data that correlates closely with the results of gene expression profiling in predicting outcome (Hans et al, Blood 103; 275–82: 2004). The t(14;18) can be detected in DLBCL, with frequencies varying between 5–40%. The aim of this study was to clarify the different mechanisms leading to Bcl-2 expression in a cohort of patients with DLBCL. Methods: The study group consisted of 94 patients with de novo DLBCL, all with a clonal karyotype at diagnosis and treated with curative intent. A TMA was constructed with duplicate 0.6mm cores and stained for Bcl-2, CD10, Bcl-6, MUM1 and FOXP1. Cases were called positive if more than 30% of the tumor cells expressed a given protein. Cases were defined as GCB if they were CD10+. Non-GCB was defined as CD10−, MUM1+ and/or FOXP1+. Cytogenetic studies were performed routinely and locus-specific FISH was performed using commercially available Vysis probes (dual-color LSI IGH/BCL2) to detect the t(14;18). Unbalanced increases in BCL2 gene copy number were determined by comparison of BCL2 and IGH signals and correlation with the karyotype. Results: The IPI was highly predictive of overall survival (OS) (p &lt; 0.00001). The t(14;18) was detected by both routine cytogenetics and FISH in 24 (25%) cases, but did not predict survival (p = 0.78). None of the non-GCB cases harbored a t(14;18). The t(14;18) and isolated BCL2 copy number gain were mutually exclusive. Expression of Bcl-2 protein and GCB-type immunostaining profile each predicted OS (p = 0.008 and 0.03, respectively). Expression of Bcl-2 was imperfectly correlated with either the t(14;18) or a non-GCB immunostaining profile, but was highly correlated with cases harboring an increased gene copy number for BCL2 (see Table, χ2 p=0.005). Increased BCL2 gene copy number did not predict OS (p = 0.43), a not unexpected finding as it accounts for only a proportion of Bcl-2 protein-positive cases. Cases lacking both the t(14;18) and increased BCL2 copy number were deemed cytogenetically “normal”, accounting for 47 cases. These were distributed between the GCB (42%) and non-GCB cases (62%). Of the cytogenetically “normal” cases, 35% of the GCB and 63% of the non-GCB expressed Bcl-2 protein. BCL2 Probe Result GCB(55) Non-GCB(39) n Bcl2 protein + n Bcl2 protein + t(14;18)(q32;21) 24 18 0 0 ⇑ Gene Copy# 8 6 15 14 “Normal” 23 8 24 15 Conclusions: We conclude that multiple mechanisms are responsible for Bcl-2 expression in DLBCL. Non-GCB cases do not harbor the t(14;18), more commonly have isolated BCL2 gene copy number gain and have a higher percentage of cytogenetically “normal” BCL2 protein-positive cases. The latter finding suggests a prominent role for transcriptional up-regulation of the BCL2 gene resulting from constitutive activation of NF- κB. DLBCL cases with a t(14;18) are always GCB and never show isolated BCL2 gene copy number gains, suggesting that these two events are mutually exclusive. The impact of other mechanisms (e.g. epigenetic changes, promoter hypomethylation) deregulating BCL2 expression requires further study. Bcl-2 protein expression and cell-of-origin (GCB vs non-GCB) are predictive biomarkers in DLBCL.

scholarly journals Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0187246 ◽  
Author(s):  
Verena Jabs ◽  
Karolina Edlund ◽  
Helena König ◽  
Marianna Grinberg ◽  
Katrin Madjar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Genome Wide ◽  
Copy Number Changes

scholarly journals Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic mice

2012 ◽  
Vol 19 (3) ◽  
pp. 409-421 ◽  
Author(s):  
Katrin-Janine Heiliger ◽  
Julia Hess ◽  
Donata Vitagliano ◽  
Paolo Salerno ◽  
Herbert Braselmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Candidate Genes ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Comparative Genomic ◽  
Ontology Term ◽  
Copy Number Changes ◽  
Chromosomal Bands

For an identification of novel candidate genes in thyroid tumourigenesis, we have investigated gene copy number changes in aTrk-T1transgenic mouse model of thyroid neoplasia. For this aim, 30 thyroid tumours fromTrk-T1transgenics were investigated by comparative genomic hybridisation. Recurrent gene copy number alterations were identified and genes located in the altered chromosomal regions were analysed by Gene Ontology term enrichment analysis in order to reveal gene functions potentially associated with thyroid tumourigenesis. In thyroid neoplasms fromTrk-T1mice, a recurrent gain on chromosomal bands 1C4–E2.3 (10.0% of cases), and losses on 3H1–H3 (13.3%), 4D2.3–E2 (43.3%) and 14E4–E5 (6.7%) were identified. The genesTwist2,Ptma,Pde6d,Bmpr1b,Pdlim5,Unc5c,Srm,Trp73,Ythdf2,Taf12andSlitrk5are located in these chromosomal bands. Copy number changes of these genes were studied by fluorescencein situhybridisation on 30 human papillary thyroid carcinoma (PTC) samples and altered gene expression was studied by qRT-PCR analyses in 67 human PTC. Copy number gains were detected in 83% of cases forTWIST2and in 100% of cases forPTMAandPDE6D. DNA losses ofSLITRK1andSLITRK5were observed in 21% of cases and ofSLITRK6in 16% of cases. Gene expression was significantly up-regulated forUNC5CandTP73and significantly down-regulated forSLITRK5in tumours compared with normal tissue. In conclusion, a global genomic copy number analysis of thyroid tumours fromTrk-T1transgenic mice revealed a number of novel gene alterations in thyroid tumourigenesis that are also prevalent in human PTCs.

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