DNA copy number profiling in microsatellite-stable and microsatellite-unstable hereditary non-polyposis colorectal cancers by targeted CNV array
DNA copy number profiling in microsatellite-stable and microsatellite-unstable hereditary non-polyposis colorectal cancers by targeted CNV array
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DOI：
10.1007/s10142-016-0532-x
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发表时间：
2017-01-01
影响因子：
2.9
通讯作者：
Shi, Daren
中科院分区：
文献类型：
--
作者：
Chen, Weixiang;Ding, Jun;Shi, Daren
大约一半符合阿姆斯特丹标准（AC）的遗传性非息肉病性结直肠癌（HNPCC）没有显示错配修复缺陷的证据，微卫星稳定（MSS）和微卫星不稳定HNPCC之间的差异仍然知之甚少。本研究采用Cytoscan HD基因芯片，比较MSS和微卫星不稳定性（MSI）的HNPCs全基因组拷贝数变异（CNV）和杂合性丢失（洛）。这是在来自复旦大学上海癌症中心（中国）的20名患有MSS HNPCC的患者和4名患有MSI HNPCC的患者的样品中进行的研究。使用一组微卫星标记检查微卫星状态。免疫组化法检测MMR表达情况。用全基因组人类CytoScan HD阵列分析肿瘤样品。检测CNV和洛。14个特异性CNV（8个增加：5p13.1、7 p13、7q22.3、8q11.21、8q12.2、19q13.11、20q11.21和20q11.23; 6个丢失：8 p22、8p23.1、8p23.1、17p13.1、17p13.2和18q21.3）与MSS HNPCC相关。在这14个CNV中，8q12.2的增加和17p13.1的丢失是新颖的。MSS肿瘤的8 q和20 q增益总长度大于MSI（P < 0.05）。HNPCC的拷贝中性洛缺失率为31.7%，MSI为29.7%，二者相似，提示未知的DNA修复基因可能参与了MSS的发生。MSS HNPCC是一个具有CNV增加的遗传特异性人群，与MSI HNPCC不同。本研究结果有助于阐明MSS HNPCC发生的遗传学基础。
About half of hereditary non-polyposis colorectal cancers (HNPCCs) fulfilling the Amsterdam criteria (AC) do not display evidence of mismatch repair defects, and the difference between microsatellite-stable (MSS) and microsatellite-unstable HNPCC remains poorly understood. The study was to compare overall copy number variation (CNV) and loss of heterozygosity (LOH) of the entire genome in HNPCCs with MSS and microsatellite-instability (MSI) using the Cytoscan HD Array. This was a study carried out in samples from 20 patients with MSS HNPCC and four patients with MSI HNPCC from the Fudan University Shanghai Cancer Center (China). The microsatellite status was examined using a panel of microsatellite markers. MMR expression status was evaluated by immunohistochemistry. Tumor samples were analyzed with the Genome-Wide Human CytoScan HD Array. CNV and LOH were determined. Fourteen specific CNVs (eight gains: 5p13.1, 7p13, 7q22.3, 8q11.21, 8q12.2, 19q13.11, 20q11.21, and 20q11.23; and six losses: 8p22, 8p23.1, 8p23.1, 17p13.1, 17p13.2, and 18q21.3) were associated with MSS HNPCC. Of these 14 CNVs, gain on 8q12.2 and loss on 17p13.1 were novel. The total length of 8q gains and 20q gains were greater in MSS tumors than in MSI (P < 0.05). The presence of similar levels of copy-neutral-LOH in MSS (31.7%) and MSI (29.7%) HNPCC suggested that unknown DNA repair genes might be involved in the tumorigenesis of MSS HNPCC. MSS HNPCC is a genetically specific population with increased CNV, which are different from MSI HNPCC. The results may help to clarify the genetic basis of MSS HNPCC tumorigenesis.