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Differential expression of selected histone modifier genes in human solid cancers

Ozdag, H; Teschendorff, AE; Ahmed, AA; Hyland, SJ; Blenkiron, C; Bobrow, L; Veerakumarasivam, A; ... Caldas, C; + view all (2006) Differential expression of selected histone modifier genes in human solid cancers. BMC GENOMICS , 7 , Article 90. 10.1186/1471-2164-7-90. Green open access

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Abstract

Background: Post-translational modification of histones resulting in chromatin remodelling plays a key role in the regulation of gene expression. Here we report characteristic patterns of expression of 12 members of 3 classes of chromatin modifier genes in 6 different cancer types: histone acetyltransferases ( HATs)- EP300, CREBBP, and PCAF; histone deacetylases ( HDACs)- HDAC1, HDAC2, HDAC4, HDAC5, HDAC7A, and SIRT1; and histone methyltransferases ( HMTs)- SUV39H1 and SUV39H2. Expression of each gene in 225 samples ( 135 primary tumours, 47 cancer cell lines, and 43 normal tissues) was analysed by QRT-PCR, normalized with 8 housekeeping genes, and given as a ratio by comparison with a universal reference RNA.Results: This involved a total of 13,000 PCR assays allowing for rigorous analysis by fitting a linear regression model to the data. Mutation analysis of HDAC1, HDAC2, SUV39H1, and SUV39H2 revealed only two out of 181 cancer samples ( both cell lines) with significant coding-sequence alterations. Supervised analysis and Independent Component Analysis showed that expression of many of these genes was able to discriminate tumour samples from their normal counterparts. Clustering based on the normalized expression ratios of the 12 genes also showed that most samples were grouped according to tissue type. Using a linear discriminant classifier and internal cross-validation revealed that with as few as 5 of the 12 genes, SIRT1, CREBBP, HDAC7A, HDAC5 and PCAF, most samples were correctly assigned.Conclusion: The expression patterns of HATs, HDACs, and HMTs suggest these genes are important in neoplastic transformation and have characteristic patterns of expression depending on tissue of origin, with implications for potential clinical application.

Type: Article
Title: Differential expression of selected histone modifier genes in human solid cancers
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-2164-7-90
Publisher version: http://dx.doi.org/10.1186/1471-2164-7-90
Language: English
Additional information: © 2006 Özdağ et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: BREAST-CANCER, CELL-LINES, PROSTATE-CANCER, METHYLATION, DEACETYLASE, MUTATIONS, CBP, ACETYLATION, PATTERNS, REPRODUCIBILITY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/127086
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