High-content analysis of cancer genome DNA alterations

Degenhardt, Yan; Wooster, Richard; McCombie, W. Richard; Lucito, Robert; Powers, Scott

doi:10.1016/j.gde.2008.01.005

Cited by 11 publications

(6 citation statements)

References 43 publications

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“…Recently, genomewide studies initiated a more comprehensive search for genomic alterations, including gene duplications, that may affect cancer development (Weir et al, 2004;Degenhardt et al, 2008). Although these studies suggest a wide role of gene duplications in cancer, the field has not yet produced reliable estimates of the total number of gene duplications that may have a role in cancers.…”

Section: Deleterious Duplicationsmentioning

confidence: 99%

Gene Dosage and Duplication

Kondrashov

2010

Evolution After Gene Duplication

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Section: Deleterious Duplicationsmentioning

confidence: 99%

Gene Dosage and Duplication

Kondrashov

2010

Evolution After Gene Duplication

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“…Copy number variations (CNV) are a common occurrence in all forms of cancer [4] , [5] , [6] , [7] , [8] , [9] . A typical cancer sample exhibits an average of 17% amplifications and 16% deletions within an entire genome.…”

Section: Introductionmentioning

confidence: 99%

Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

et al. 2011

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The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates.

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“…This has profound implications for distinctions between cancer and normal cells, which differ significantly in the expression levels of particular genes. The characterization of extensive epigenetic changes – in DNA methylation, histone modification and nucleosome remodeling – associated with oncogenesis (11,12) and the ability to elucidate genome‐wide mutational profiles for specific carcinomas (13,14) suggests now looking within chromatin for new drug targets that correspond to vulnerable points of cancer cells.…”

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confidence: 99%

Chromatin – a New, Old Drug Target?

Davey

Davey²

2008

Chem Biol Drug Des

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Chromatin is the therapeutic target for DNA-binding medicinal agents, yet we know substantially more about the interaction of drugs with naked DNA. Current research is unraveling a dynamic gene- and transcription state-dependent structure for human chromatin and also unveiling differences in nucleosome positioning between cancer and normal cells. Considering observations on the modulation of DNA drug binding and adduct repair by histone packaging suggests potential for targeting specific sites within nucleosomes that coincide with weak points of cancer cells.

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High-content analysis of cancer genome DNA alterations

Cited by 11 publications

References 43 publications

Gene Dosage and Duplication

Gene Dosage and Duplication

Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

Chromatin – a New, Old Drug Target?

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