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Genome-wide somatic copy number alteration analysis and database construction for cervical cancer

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Abstract

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.

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Funding

This work was supported by a grant from the National Natural Science Foundation of China (Grant Nos. U1603120, 31571314, 31771394).

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  1. Hong Luo and Xiaohan Xu contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Bio-Resources and Eco-Environment, Center of Growth, Metabolism, and Aging, College of Life Sciences, Sichuan University, Chengdu, 610064, China

    Hong Luo, Jian Yang, Kun Wang, Chen Wang & Haoyang Cai

  2. Department of Obstetrics and Gynecology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832002, China

    Xiaohan Xu & Ping Yang

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  1. Hong Luo
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  2. Xiaohan Xu
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  3. Jian Yang
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Contributions

HC and PY conceived the study. HL, XX, JY, KW and CW contributed to data collection. HL and XX carried out the analysis. JY, KW and CW assisted with all the statistical analysis. HC and PY wrote the draft of the manuscript. All authors discussed the results and contributed to the final manuscript.

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Correspondence to Ping Yang or Haoyang Cai.

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Communicated by Stefan Hohmann.

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Luo, H., Xu, X., Yang, J. et al. Genome-wide somatic copy number alteration analysis and database construction for cervical cancer. Mol Genet Genomics 295, 765–773 (2020). https://doi.org/10.1007/s00438-019-01636-x

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