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Genes with relevance for early to late progression of colon carcinoma based on combined genomic and transcriptomic information from the same patients.

Journal article
Authors Kristina Lagerstedt
Erik Kristiansson
Christina Lönnroth
Marianne Andersson
Britt-Marie Iresjö
Annika Gustafsson Asting
Elisabeth Hansson
Ulf Kressner
Svante Nordgren
Fredrik Enlund
Kent Lundholm
Published in Cancer informatics
Volume 9
Pages 79-91
ISSN 1176-9351
Publication year 2010
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Pages 79-91
Language en
Keywords CGH array, colorectal cancer, microRNA, transcription
Subject categories Cancer and Oncology, Surgery


BACKGROUND: Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. METHODS: Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. RESULTS: Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A-D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. CONCLUSIONS: Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes.

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