Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer

Bermudo, Raquel; Abia, David; Ferrer, Berta; Nayach, Iracema; Benguría, Alberto; Zaballos, Ángel; Rey, Javier del; Miró, Rosa; Campo, Elı́as; Martı́nez-A, Carlos; Ortíz, Ángel R.; Fernández, Pedro; Thomson, Timothy M.

doi:10.1186/1471-2407-8-315

Cited by 9 publications

(20 citation statements)

References 39 publications

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“…The most discriminant model generated for such samples contained six genes, all previously associated with cancer, which confers our signature an additional functional relevance (Tomlins et al , 2007; Bermudo et al , 2008). This model showed 92.6% concordance between the molecular profiling of needle washes and the histopathological diagnosis of the corresponding biopsy cylinders.…”

Section: Discussionmentioning

confidence: 99%

Highly sensitive molecular diagnosis of prostate cancer using surplus material washed off from biopsy needles

et al. 2011

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Introduction:Currently, final diagnosis of prostate cancer (PCa) is based on histopathological analysis of needle biopsies, but this process often bears uncertainties due to small sample size, tumour focality and pathologist's subjective assessment.Methods:Prostate cancer diagnostic signatures were generated by applying linear discriminant analysis to microarray and real-time RT–PCR (qRT–PCR) data from normal and tumoural prostate tissue samples. Additionally, after removal of biopsy tissues, material washed off from transrectal biopsy needles was used for molecular profiling and discriminant analysis.Results:Linear discriminant analysis applied to microarray data for a set of 318 genes differentially expressed between non-tumoural and tumoural prostate samples produced 26 gene signatures, which classified the 84 samples used with 100% accuracy. To identify signatures potentially useful for the diagnosis of prostate biopsies, surplus material washed off from routine biopsy needles from 53 patients was used to generate qRT–PCR data for a subset of 11 genes. This analysis identified a six-gene signature that correctly assigned the biopsies as benign or tumoural in 92.6% of the cases, with 88.8% sensitivity and 96.1% specificity.Conclusion:Surplus material from prostate needle biopsies can be used for minimal-size gene signature analysis for sensitive and accurate discrimination between non-tumoural and tumoural prostates, without interference with current diagnostic procedures. This approach could be a useful adjunct to current procedures in PCa diagnosis.

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Section: Discussionmentioning

confidence: 99%

Highly sensitive molecular diagnosis of prostate cancer using surplus material washed off from biopsy needles

et al. 2011

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“…In a previous study, 23 we performed a transcriptomic analysis of prostate samples with the aim of finding gene expression changes in the tumoral glands that correlated with chromosomal abnormalities in the tumors. When performing transcriptional analysis with prostate samples, the high degree of tissue heterogeneity is a very important aspect to be taken into account, since it can lead to confounding results, highlighting genes whose differential expression is only the consequence of the different representation of cell compartments between benign and tumoral samples.…”

Section: Identification Of a Recurrent Gain In Pca By The Coordinate mentioning

confidence: 99%

“…Our transcriptomic analysis by FADA also allowed the identification of the 318 genes showing the most significant differential expression between normal and tumoral tissues. One‐hundred thirty four were overexpressed and 184 underexpressed in tumoral versus normal prostate tissues 23 …”

Section: Identification Of a Recurrent Gain In Pca By The Coordinate mentioning

confidence: 99%

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Discovery of genomic alterations through coregulation analysis of closely linked genes: a frequent gain in 17q25.3 in prostate cancer

Bermudo

Abia

Benitez

et al. 2010

Annals of the New York Academy of Sciences

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Despite its high incidence as the second most common tumor in males worldwide, primary prostate cancer has been associated with few recurrent chromosomal gains and deletions that are consistent across various studies. Few studies have explored how chromosomal alterations are coupled to abnormal gene expression. Here, we review the major genomic aberrations associated with prostate cancer and describe how detailed transcriptional and computational analyses allowed us to discover a recurrent chromosomal gain in a small region on chromosome 17. Fluorescent in situ hybridization confirmed the presence of a copy number gain in 17q25.3 in tumor-associated preneoplastic lesions of the prostate, 65% of primary tumors, and metastatic samples. These results suggest the involvement of this gain at all steps of prostate cancer progression.

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“…The analysis of tumor tissues offers insight into contributions by both epithelial and stomal components; however, the presence of fibroblasts, inflammatory cells, and vascular endothelial cells increases the complexity in interpreting expressed gene patterns and must be taken into account when performing high-throughput analyses. Moreover, representation of each cell type within a given sample determines the overall expression profile and makes it difficult to compare prostate samples with varying epithelial and stromal contents (24). In this study we established primary cell strains from radical prostatectomy specimens of AA and EA men, which were matched for tumor stage and Gleason's grade.…”

Section: Introductionmentioning

confidence: 99%

Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

Dritschilo¹

2009

Int J Oncol

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Abstract. African-American (AA) men experience an increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with the potential to predispose AA men to prostate tumor progression and metastasis. To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Quantitative RT-PCR and immunohistochemistry validated mRNA and protein expression levels. RNAi knockdowns provided support for biological significance for the identified genes in prostate cancer cells. Son of sevenless homolog 1 (SOS1) was overexpressed in AA male-derived primary prostate cancer epithelial cells. Depletion of SOS1 in PC3 and DU145 prostate cancer cells resulted in decreased capacities for cell proliferation, migration and invasion, at least partially through inhibition of extracellular signal-regulated kinase 1 and 2. Tissue microarray analyses of SOS1 expression in prostate carcinomas correlated with Gleason's grades of tumors, consistent with a possible role in prostate cancer progression. Investigation of prostate cancer-derived epithelial cells has led to identification of SOS1 as a potential candidate biomarker and molecular therapeutic target in prostate cancer in AA men, consistent with the hypothesis that a biological basis exists for prostate cancer aggressiveness in AA men.

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Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer

Cited by 9 publications

References 39 publications

Highly sensitive molecular diagnosis of prostate cancer using surplus material washed off from biopsy needles

Highly sensitive molecular diagnosis of prostate cancer using surplus material washed off from biopsy needles

Discovery of genomic alterations through coregulation analysis of closely linked genes: a frequent gain in 17q25.3 in prostate cancer

Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

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