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Visualizing Chromosomes as Transcriptome Correlation Maps: Evidence of Chromosomal Domains Containing Co-expressed Genes—A Study of 130 Invasive Ductal Breast Carcinomas

¹ Unité Mixte de Recherche 144, Centre National de la Recherche Scientifique; Departments of ² Surgery, ³ Tumor Biology, ⁴ Biostatistics, ⁵ Radiotherapy, ⁶ Medical Oncology, and ⁷ Translational Research; and ⁸ U509, Institut National de la Santé et de la Recherche Médicale, Institut Curie, Paris, France and ⁹ Astra Zeneca, Alderley Park, United Kingdom

Requests for reprints: François Radvanyi, Unité Mixte de Recherche 144, Institut Curie-CNRS, 26 rue d'Ulm, 75248 Paris Cedex 05, France. Phone: 33-1-42-34-63-39; Fax: 33-1-42-34-63-49; E-mail: francois.radvanyi{at}curie.fr.

Completion of the working draft of the human genome has made it possible to analyze the expression of genes according to their position on the chromosomes. Here, we used a transcriptome data analysis approach involving for each gene the calculation of the correlation between its expression profile and those of its neighbors. We used the U133 Affymetrix transcriptome data set for a series of 130 invasive ductal breast carcinomas to construct chromosomal maps of gene expression correlation (transcriptome correlation map). This highlighted nonrandom clusters of genes along the genome with correlated expression in tumors. Some of the gene clusters identified by this method probably arose because of genetic alterations, as most of the chromosomes with the highest percentage of correlated genes (1q, 8p, 8q, 16p, 16q, 17q, and 20q) were also the most frequent sites of genomic alterations in breast cancer. Our analysis showed that several known breast tumor amplicons (at 8p11-p12, 11q13, and 17q12) are located within clusters of genes with correlated expression. Using hierarchical clustering on samples and a Treeview representation of whole chromosome arms, we observed a higher-order organization of correlated genes, sometimes involving very large chromosomal domains that could extend to a whole chromosome arm. Transcription correlation maps are a new way of visualizing transcriptome data. They will help to identify new genes involved in tumor progression and new mechanisms of gene regulation in tumors.

Key Words: Ductal breast carcinoma • transcription correlation map • DNA microarrays

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