Genomic instability and DNA ploidy are linked to DNA copy number aberrations of 8p23 and 22q11.23 in gastric cancers.
Genomic instability and DNA ploidy are linked to DNA copy number aberrations of 8p23 and 22q11.23 in gastric cancers.
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DOI：
10.3892/ijmm_00000470
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发表时间：
2010-09
影响因子：
5.4
通讯作者：
S. Kawauchi;Tomoko Furuay;T. Uchiyama;A. Adachi;Takae Okada;Motonao Nakao;A. Oga;Kenichiro Uchida;K. Sasaki
中科院分区：
文献类型：
--
作者：
S. Kawauchi;Tomoko Furuay;T. Uchiyama;A. Adachi;Takae Okada;Motonao Nakao;A. Oga;Kenichiro Uchida;K. Sasaki
染色体不稳定性（CIN）与非整倍体的关系已被报道。本研究的目的是鉴定胃癌中存在的CIN和非整倍体的基因组畸变。对27例散发性胃腺癌分别采用荧光原位杂交（FISH）和图像细胞术检测CIN阳性肿瘤和DNA倍体。此外，使用基于阵列的比较基因组杂交来鉴定细菌人工染色体克隆，其在CIN阳性和CIN阴性肿瘤之间以及非整倍体和二倍体肿瘤之间显示拷贝数畸变频率的差异。许多染色体区域存在DNA拷贝数畸变，其中一些是与CIN表型和非整倍体相关的非随机畸变。22q11.23拷贝数丢失在CIN阳性癌症中比其他癌症更常见（7/12 vs. 2/15，p<0.01），在非整倍体癌症中比二倍体癌症更常见（8/16 vs. 1/11，p<0.05）。22q11.23丢失的频率在CIN阳性和非整倍体肿瘤之间以及在CIN阴性和二倍体肿瘤之间存在显著差异（7/10 vs. 1/9，p<0.01）。相反，在9个CIN阴性/二倍体癌症中的6个中检测到8p23.2的DNA拷贝数增加，但在CIN阳性/非整倍体癌症中未检测到8p23.2的DNA拷贝数增加（p<0.01）。没有癌症携带两种畸变（22q11.23丢失和8p23.2获得）。目前的研究表明，22q11.23丢失和8p23.2增加是CIN和非整倍体的标志。这是第一份报告描述了胃癌中22q11.23丢失和8p23.2获得之间的基因组不稳定性和DNA倍体的负相关关系。
The close relationship between chromosomal instability (CIN) and aneuploidy has been reported. The purpose of this study was to identify genomic aberrations present with CIN and aneuploidy in gastric cancers. FISH and image cytometry were applied to 27 sporadic gastric adenocarcinomas to identify CIN-positive tumors and to determine DNA ploidy, respectively. In addition, array-based comparative genomic hybridization was used to identify bacterial artificial chromosome clones that displayed differences in the frequency of copy number aberrations between CIN-positive and CIN-negative tumors, and between aneuploid and diploid tumors. There were many chromosomal regions with DNA copy number aberrations, some of which were nonrandom aberrations linked to the CIN phenotype and aneuploidy. A copy number loss of 22q11.23 was more frequent in CIN-positive cancers than in others (7/12 vs. 2/15, p<0.01) and in aneuploid cancers than in diploid cancers (8/16 vs. 1/11, p<0.05). The frequency of 22q11.23 loss differed significantly between CIN-positive and aneuploid tumors and between CIN-negative and diploid cancers (7/10 vs. 1/9, p<0.01). In contrast, a DNA copy number gain of 8p23.2 was detected in 6 out of 9 CIN-negative/diploid cancers, but was not detected in CIN-positive/aneuploid cancers (p<0.01). There were no cancers carrying both aberrations (22q11.23 loss and 8p23.2 gain). The present study indicates that a 22q11.23 loss and a 8p23.2 gain are markers for both CIN and aneuploidy. This is the first report describing an inverse relationship between the 22q11.23 loss and 8p23.2 gain in terms of genomic instability and DNA ploidy in gastric cancers.