Differential expression of selected histone modifier genes in human solid cancers

Autor: Cherie Blenkiron, Linda Bobrow, Hilal Özdağ, Carlos Caldas, Mark J. Arends, Tanya Subkhankulova, V. Peter Collins, Sarah J Hyland, Ahmed Ashour Ahmed, Abhi Veerakumarasivam, Andrew E. Teschendorff, David D.L. Bowtell, James D. Brenton, Glynn Burtt, Tony Kouzarides
Přispěvatelé: Collins, Peter [0000-0002-0381-8516], Kouzarides, Tony [0000-0002-8918-4162], Brenton, James [0000-0002-5738-6683], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Male
DNA
Complementary
Lung Neoplasms
lcsh:QH426-470
lcsh:Biotechnology
Breast Neoplasms
Biology
Polymerase Chain Reaction
Chromatin remodeling
Gene Expression Regulation
Enzymologic
Histone Deacetylases
Histones
lcsh:TP248.13-248.65
Neoplasms
Histone methylation
Histone H2A
Genetics
Histone code
Cluster Analysis
Humans
Protein Methyltransferases
Polymorphism
Single-Stranded Conformational
Epigenomics
Histone Acetyltransferases
Regulation of gene expression
Ovarian Neoplasms
Carcinoma
DNA
Neoplasm
Histone-Lysine N-Methyltransferase
Molecular biology
Housekeeping gene
Neoplasm Proteins
Gene Expression Regulation
Neoplastic
Histone Code
Pancreatic Neoplasms
lcsh:Genetics
Cell Transformation
Neoplastic
Histone methyltransferase
Histone Methyltransferases
Linear Models
Female
Colorectal Neoplasms
Protein Processing
Post-Translational
Research Article
Biotechnology
Zdroj: Ozdağ, H, Teschendorff, A E, Ahmed, A A, Hyland, S J, Blenkiron, C, Bobrow, L, Veerakumarasivam, A, Burtt, G, Subkhankulova, T, Arends, M J, Collins, V P, Bowtell, D, Kouzarides, T, Brenton, J D & Caldas, C 2006, ' Differential expression of selected histone modifier genes in human solid cancers ', BMC Genomics, vol. 7, pp. 90 . https://doi.org/10.1186/1471-2164-7-90
BMC Genomics, Vol 7, Iss 1, p 90 (2006)
BMC Genomics
ISSN: 1471-2164
DOI: 10.1186/1471-2164-7-90
Popis: BackgroundPost-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, andPCAF; histone deacetylases (HDACs)-HDAC1, HDAC2, HDAC4, HDAC5, HDAC7A, andSIRT1; and histone methyltransferases (HMTs)-SUV39H1andSUV39H2. Expression of each gene in 225 samples (135 primary tumours, 47 cancer cell lines, and 43 normal tissues) was analysedby QRT-PCR, normalized with 8 housekeeping genes, and given as a ratio by comparison with a universal reference RNA.ResultsThis involved a total of 13,000 PCR assays allowing for rigorous analysis by fitting a linear regression model to the data. Mutation analysis ofHDAC1, HDAC2, SUV39H1, andSUV39H2revealed 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, HDAC5andPCAF, most samples were correctly assigned.ConclusionThe 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.
Databáze: OpenAIRE
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