Amplification of the ch19p13.2 NACC1 locus in ovarian high-grade serous carcinoma.
Amplification of the ch19p13.2 NACC1 locus in ovarian high-grade serous carcinoma.
复制标题
DOI：
10.1038/modpathol.2010.230
复制
发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
基于数字核型分析，我们已经确定了一个新的，离散的扩增区域在ch19p13.2在高级别卵巢浆液性癌。为了进一步表征该区域，我们通过分析来自癌症基因组图谱（TCGA）的341例高级别浆液性癌来确定ch19p13.2扩增的频率和生物学意义，并发现在18%的病例中该位点的DNA拷贝数增加。我们通过分析所有扩增基因的TCGA数据集来关联DNA和RNA拷贝数，并在ch19p13.2内检测到7个显著相关的基因（R ≥0.54），事实上，这些基因被列为全基因组范围内前100个潜在的“驱动”基因。有趣的是，编码NAC1的7个基因之一NACC1先前被报道参与卵巢浆液性癌中肿瘤复发的发展，并在紫杉醇耐药的发展中发挥因果作用。因此，我们选择NACC 1在独立队列中进行验证。基于荧光原位杂交，我们发现175例高级别浆液性癌中有35例（20%）NACC1基因座的DNA拷贝数增加，这些扩增的病例与6个月内的早期疾病复发相关（p= 0.013）。与未扩增的肿瘤相比，在扩增的肿瘤中检测到基于免疫组织化学的显著高水平的NAC 1蛋白表达（p< 0.005）。总之，我们的数据表明，扩增在ch19p13.2 NACC1基因座，导致NAC1过表达，是与卵巢癌早期肿瘤复发相关的分子遗传学改变之一。
Based on digital karyotyping, we have identified a new, discrete amplified region at ch19p13.2 in a high-grade ovarian serous carcinoma. To further characterize this region, we determined the frequency and biological significance of ch19p13.2 amplification by analyzing 341 high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) and found an increased DNA copy number at this locus in 18% of cases. We correlated the DNA and RNA copy number by analyzing the TCGA dataset for all amplified genes and detected 7 genes within ch19p13.2 that were significantly correlated (R ≥0.54) and were, in fact, listed as the top 100 potential “driver” genes at a genome-wide scale. Interestingly, one of the 7 genes, NACC1, encoding NAC1 was previously reported to be involved in the development of tumor recurrence in ovarian serous carcinoma and to play a causal role in the development of paclitaxel resistance. Therefore, we selected NACC1 for validation in an independent cohort. Based on fluorescence in situ hybridization, we found that 35 (20%) of 175 high-grade serous carcinomas had an increased DNA copy number at the NACC1 locus, and those amplified cases were associated with early disease recurrence within 6 months (p= 0.013). A significantly high level of NAC1 protein expression based on immunohistochemistry was detected in amplified tumors as compared to non-amplified tumors (p< 0.005). In summary, our data suggest that amplification at the ch19p13.2 NACC1 locus, leading to NAC1 overexpression, is one of the molecular genetic alterations associated with early tumor recurrence in ovarian cancer.
登录
查看更多内容
影响因子：
11.2
作者：
Kuo KT;Guan B;Feng Y;Mao TL;Chen X;Jinawath N;Wang Y;Kurman RJ;Shih IeM;Wang TL
通讯作者：
Wang TL
影响因子：
--
作者：
Ueda SM;Yap KL;Davidson B;Tian Y;Murthy V;Wang TL;Visvanathan K;Kuhajda FP;Bristow RE;Zhang H;Shih IeM
通讯作者：
Shih IeM
影响因子：
3.6
作者：
Nakayama, Kentaro;Nakayama, Naomi;Wang, Tian-Li
通讯作者：
Wang, Tian-Li
影响因子：
11.2
作者：
Park, Joon T.;Li, Mei;Wang, Tian-Li
通讯作者：
Wang, Tian-Li
影响因子：
11.2
作者：
Nakayama, Kentaro;Nakayama, Naomi;Shih, Ie-Ming
通讯作者：
Shih, Ie-Ming