Abstract
Purpose: Chromosomal instability (CIN), microsatellite instability (MIN), and CpG island methylation phenotype (CIMP) are known processes through which colorectal cancer (CRC) can occur. In a given tumor, one or more of these events might be responsible for tumor development. We previously reported the results of our MSI and CIMP analysis of colorectal tumors in African Americans (AA), a group at high risk. Here, we report our array comparative genomic hybridization (aCGH) population analysis of AA and Caucasian CRC and its implication for the understanding of CRC development in this population.
Experimental design: We used 30 AA and 22 Caucasian CRC patients and applied aCGH (105k chip) to identify copy number aberrations in samples. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer candidate genes (CAN genes). Bioinformatics analysis was done to calculate the chromosomal imbalance using Agilent Genomic Workbench 5.0.
Results: There was an average of 30 aberrations per patient with all samples displaying some level of chromosomal instability. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to alterations in Caucasians.
Conclusions: Prominent chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were the primary targets in AAs. Most CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. CIN seems to be more prominent in AAs and may play a distinctive role in CRC development in this population.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B52.
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