Genome-wide somatic copy number alteration analysis and database construction for cervical cancer
Genome-wide somatic copy number alteration analysis and database construction for cervical cancer
复制标题
宫颈癌全基因组体细胞拷贝数改变分析和数据库构建。
DOI：
10.1007/s00438-019-01636-x
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发表时间：
2020-01-04
影响因子：
3.1
通讯作者：
Cai，Haoyang
中科院分区：
文献类型：
--
作者：
Luo，Hong;Xu，Xiaohan;Cai，Haoyang
宫颈癌是妇科常见的恶性肿瘤，发病率高，死亡率高。体细胞拷贝数改变(CNA)在识别抑癌基因和癌基因方面发挥着重要作用，是许多癌症类型的有用诊断指标。然而，CNA在宫颈癌中的基因组图谱还没有得到全面的描述。在本研究中，我们从不同的数据来源收集了974份宫颈癌样本。所有样品通过基因组阵列进行分析，获得高分辨率的CNA。用GISTIC2.0确定具有CNA事件的焦点基因组区域和潜在的癌症驱动基因。同时，我们使用PHP和自编的Perl和R脚本构建了一个全面的宫颈癌数据库。总共检测到54个重复的扩增和缺失区域。在这些区域发现了频繁改变的抑癌基因，包括PIK3CA、ERBB2、EP300和FBXW7。还确定了CNA热点和相关丰富的功能类别。结果表明，子宫颈癌中染色体断裂发生率为6.06%，并检测了染色体粉碎性热点区域。基于整理的数据，我们开发了一个关于宫颈癌拷贝数改变的综合数据库CNAdbCC(http://cailab.labshare.cn/CNAdbCC/)，)。我们为数据挖掘和可视化提供了一个用户友好的Web界面。这是专门研究宫颈癌基因组改变的最全面的公共数据库。这些结果扩展了我们对宫颈癌的分子理解。该数据库将使研究人员能够探索这种致命癌症的特定CNA模式，并促进发现治疗候选药物。
Cervical cancer is a common gynecological malignancy with high incidence and mortality. Somatic copy number alterations (CNAs) play an important role in identifying tumor suppressor genes and oncogenes and are a useful diagnostic indicator for many cancer types. However, the genomic landscape of CNAs in cervical cancer has not yet been comprehensively characterized. In the present study, we collected 974 cervical cancer samples from different data sources. All samples were analyzed by genomic arrays to obtain high-resolution CNAs. Focal genomic regions with CNA events and potential cancer driver genes were identified by GISTIC2.0. Meanwhile, we constructed a comprehensive cervical cancer database by PHP and self-written Perl and R scripts. In total, 54 recurrent regions of amplification and deletion were detected. Frequently altered tumor suppressor genes were found in these regions, including PIK3CA, ERBB2, EP300 and FBXW7. CNA hotspots and related enriched functional categories were also identified. The incidence of chromothripsis in cervical cancer was estimated to be 6.06%, and the chromosome pulverization hotspot regions were detected. Based on the curated data, we developed CNAdbCC (http://cailab.labshare.cn/CNAdbCC/), a comprehensive database for copy number alterations in cervical cancer. We provide a user-friendly Web interface for data mining and visualization. It is the most comprehensive public database devoted exclusively to genomic alterations in cervical cancer. These results extend our molecular understanding of cervical cancer. The database will enable researchers to explore specific CNA patterns in this lethal cancer and facilitate the discovery of therapeutic candidates.