Distinct genetic alterations in colorectal cancer.
BACKGROUND
Colon 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.


RESULTS
We 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
Chromosome 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.
Ashktorab
Hassan
H
Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America. hashktorab@howard.edu
Schäffer
Alejandro A
AA
Daremipouran
Mohammad
M
Smoot
Duane T
DT
Lee
Edward
E
Brim
Hassan
H
D000368:Aged; D000369:Aged, 80 and over; D043171:Chromosomal Instability; D002877:Chromosomes, Human; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization