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Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer.

Journal article
Authors Annika Gustafsson Asting
Kristina Lagerstedt
Erik Kristiansson
Christina Lönnroth
Marianne Andersson
Elham Rekabdar
Elisabeth Hansson
Ulf Kressner
Fredrik Enlund
Kent Lundholm
Published in Journal of Cancer Therapy
Volume 5
Issue 14
ISSN 2151-1934
Publication year 2014
Published at Institute of Clinical Sciences, Department of Surgery
Department of Mathematical Sciences, Mathematical Statistics
Language en
Links dx.doi.org/10.4236/jct.2014.514135
Keywords Copy Number Variation, DNA, Array CGH, Colorectal Cancer
Subject categories Cancer and Oncology

Abstract

Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer; these DNA alterations may have been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.

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