Distinct Genetic Alterations in Colorectal Cancer |
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Authors: | Hassan Ashktorab Alejandro A Sch?ffer Mohammad Daremipouran Duane T Smoot Edward Lee Hassan Brim |
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Institution: | 1. Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America.; 2. National Center for Biotechnology Information, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland, United States of America.; 3. Department of Pathology, Howard University, College of Medicine, Washington, DC, United States of America.;Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Germany |
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Abstract: | BackgroundColon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities.Methodology/Principal FindingsWe applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. 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 Caucasian alterations.Conclusions/SignificanceChromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some 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. The observed CIN may play a distinctive role in CRC in AAs. |
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