Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America.
PLoS One. 2010 Jan 26;5(1):e8879. doi: 10.1371/journal.pone.0008879.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
结肠癌（CRC）的发展通常包括染色体不稳定性（CIN），导致大的 DNA 片段的扩增和缺失。流行病学、临床和细胞遗传学研究表明，非裔美国人和白种人患者的 CRC 肿瘤之间存在相当大的差异。在这项研究中，我们确定了非裔美国人散发性 CRC 肿瘤中的基因组拷贝数异常，以调查观察到的差异的可能解释。
方法/主要发现：我们应用全基因组阵列比较基因组杂交（aCGH），使用 105k 芯片来识别来自 15 名非裔美国人样本中的拷贝数异常。此外，我们还进行了与白种人的 aCGH 数据的人群比较分析，以及与广泛公布的结肠癌基因（CAN 基因）列表的分析。每个患者的平均异常数为 20 个，扩增多于缺失。对经常改变的染色体的 DNA 拷贝数进行分析显示，缺失主要发生在染色体 4、8 和 18 上。染色体 7、8、13、20 和 X 上的染色体复制发生率超过 50%。与白种人的改变相比，CIN 谱显示出一些差异。
结论/意义：男性患者的染色体 X 扩增和非裔美国人的染色体 4、8 和 18 缺失是突出的异常。一些 CAN 基因在非裔美国人中以高频改变，其中 EXOC4、EPHB6、GNAS、MLL3 和 TBX22 是最常缺失的基因，HAPLN1、ADAM29、SMAD2 和 SMAD4 是最常扩增的基因。观察到的 CIN 可能在非裔美国人的 CRC 中发挥独特的作用。
