Yang Sang Hwa, Seo Min Young, Jeong Ha Jin, Jeung Hei-Cheul, Shin Jihye, Kim Sang Chul, Noh Sung Hoon, Chung Hyun Cheol, Rha Sun Young
Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-ku, Seoul 120-752, Korea.
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):612-20.
This study examined the gene copy number change events at chromosome 20 in gastric cancer, and their possible relationship with recurrence using cDNA microarray-based comparative genomic hybridization.
Thirty pairs of gastric tumor and normal gastric tissues were used in the cDNA microarray-based comparative genomic hybridization. The cDNA microarrays containing 17,000 sequence-verified human gene probes were used in a direct comparison design, where genomic DNAs from the normal and tumor tissues were labeled with fluorescent dyes Cy3 and Cy5, respectively, and cohybridized. Genes with log(2) (Cy5/Cy3) > or = 0.58 in at least one case were selected as the amplified genes. In order to search for the association between gene copy number changes and the recurrence status, patients were grouped according to their recurrence status. Gene selection between the two groups was done, and each patient was given a score based on the sum of the selected genes' ratios. Logistic regression analysis was carried out in order to determine if the score of a group of patients was correlated with a recurrence.
A group of genes including NCOA6, CYP24A1, PTPN1, and ZNF217 was amplified in gastric cancer. Another group of 39 genes, whose sum of copy number change levels was significantly associated with a poor prognosis for recurrence, was selected (P < 0.05).
Ninety-six amplified genes at chromosome 20 of gastric cancer are reported. A scoring system based on gene copy changes at chromosome 20 can provide an independent patient grouping system that can distinguish patient recurrence status and survival.
本研究采用基于cDNA微阵列的比较基因组杂交技术，检测胃癌中20号染色体上的基因拷贝数变化事件，及其与复发的可能关系。
采用30对胃癌组织和正常胃组织进行基于cDNA微阵列的比较基因组杂交。使用含有17000个经序列验证的人类基因探针的cDNA微阵列进行直接比较设计，其中正常组织和肿瘤组织的基因组DNA分别用荧光染料Cy3和Cy5标记，并进行共杂交。在至少1例中log(2)(Cy5/Cy3)≥0.58的基因被选为扩增基因。为了寻找基因拷贝数变化与复发状态之间的关联，根据患者的复发状态进行分组。在两组之间进行基因筛选，并根据所选基因比率的总和为每个患者打分。进行逻辑回归分析以确定一组患者的得分是否与复发相关。
包括NCOA6、CYP24A1、PTPN1和ZNF217在内的一组基因在胃癌中发生扩增。另外选择了一组39个基因，其拷贝数变化水平总和与复发预后不良显著相关(P<0.05)。
报道了胃癌20号染色体上的96个扩增基因。基于20号染色体基因拷贝变化的评分系统可以提供一个独立的患者分组系统，能够区分患者的复发状态和生存情况。
