TITLE:
Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer
AUTHORS:
Annika Gustafsson Asting, Kristina K. Lagerstedt, Erik Kristiansson, Christina Lönnroth, Marianne Andersson, Elham Rekabdar, Elisabeth Hansson, Ulf Kressner, Fredrik Enlund, Kent Lundholm
KEYWORDS:
Copy Number Variation, DNA, Array CGH, Colorectal Cancer
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.14,
December
3,
2014
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.