Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans

The lager yeasts, Saccharomyces pastorianus, are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus and are divided into two broad groups, Group I and II. The two groups evolved from at least one common hybridisation event but have subsequently diverged with Group I strains losing many S. cerevisiae chromosomes while the Group II strains retain both sub-genomes. The complex genomes, containing orthologous alleles from the parental chromosomes, pose interesting questions regarding gene regulation and its impact on the fermentation properties of the strains. Superimposed on the presence of orthologous alleles are complexities of gene dosage due to the aneuploid nature of the genomes. We examined the contribution of the S. cerevisiae and S. eubayanus alleles to the gene expression patterns of Group I and II strains during fermentation. We show that the relative expression of S. cerevisiae and S. eubayanus orthologues is positively correlated with gene copy number. Despite the reduced S. cerevisiae content in the Group I strain, S. cerevisiae orthologues contribute to biochemical pathways upregulated during fermentation which may explain the retention of specific chromosomes in the strain. Conversely, S. eubayanus genes are significantly overrepresented in the upregulated gene pool in the Group II strain. Comparison of the transcription profiles of Group I and II strains during fermentation identified both common and unique gene expression patterns, with gene copy number being a dominant contributory factor. Thus, the aneuploid genomes create complex patterns of gene expression during fermentation with gene dosage playing a crucial role both within and between strains.

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

Genes Chromosomes and Cancer ◽

10.1002/gcc.20475 ◽

2007 ◽

Vol 46 (10) ◽

pp. 895-908 ◽

Cited By ~ 13

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

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

PLoS ONE ◽

10.1371/journal.pone.0187246 ◽

2017 ◽

Vol 12 (11) ◽

pp. e0187246 ◽

Cited By ~ 14

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

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

Endocrine Related Cancer ◽

10.1530/erc-11-0387 ◽

2012 ◽

Vol 19 (3) ◽

pp. 409-421 ◽

Cited By ~ 15

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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Gene copy number changes in dermatofibrosarcoma protuberans – a fine-resolution study using array comparative genomic hybridization

Cytogenetic and Genome Research ◽

10.1159/000095925 ◽

2006 ◽

Vol 115 (3-4) ◽

pp. 283-288 ◽

Cited By ~ 10

Author(s):

S. Kaur ◽

H. Vauhkonen ◽

T. Böhling ◽

F. Mertens ◽

N. Mandahl ◽

...

Keyword(s):

Comparative Genomic Hybridization ◽

Copy Number ◽

Array Comparative Genomic Hybridization ◽

Gene Copy Number ◽

Dermatofibrosarcoma Protuberans ◽

Gene Copy ◽

Comparative Genomic ◽

Copy Number Changes ◽

Fine Resolution ◽

Resolution Study

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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

Journal of Clinical Oncology ◽

10.1200/jco.2009.24.6611 ◽

2010 ◽

Vol 28 (13) ◽

pp. 2174-2180 ◽

Cited By ~ 89

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.

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