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

Journal of Cancer Therapy 2014年第14期5卷 1354-1361页

作者： annika gustafsson asting Kristina K.Lagerstedt Erik Kristiansson Christina Lonnroth Marianne Andersson Elham Rekabdar Elisabeth Hansson Ulf Kressner Fredrik Enlund Kent Lundholm Department of Surgery Surgical Metabolic Research LaboratorySahlgrenska University HospitalUniversity of GothenburgGothenburgSweden Department of Mathematical Sciences Mathematical StatisticsChalmers University of TechnologyGothenburgSweden Genomics Core Facility Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden Department of Surgery Uddevalla HospitalUddevallaSweden Department of Surgery Danderyds HospitalStockholmSweden Department of Surgery South HospitalStockholmSweden Department of Clinical Chemistry Sahlgrenska University HospitalUniversity of GothenburgGothenburgSweden

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.

关键词： Copy Number Variation DNA Array CGH Colorectal Cancer

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