Integrated genomic and molecular characterization of cervical cancer

被引：0

作者：

机构：

[1] Albert Einstein College of Medicine,

[2] Bronx,undefined

[3] Analytical Biological Services,undefined

[4] Inc.,undefined

[5] Barretos Cancer Hospital,undefined

[6] Baylor College of Medicine,undefined

[7] Beckman Research Institute of City of Hope,undefined

[8] Buck Institute for Research on Aging,undefined

[9] Canada’s Michael Smith Genome Sciences Centre,undefined

[10] BC Cancer Agency,undefined

[11] Harvard Medical School,undefined

[12] Helen F. Graham Cancer Center and Research Institute at Christiana Care Health Services,undefined

[13] Inc.,undefined

[14] HudsonAlpha Institute for Biotechnology,undefined

[15] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University,undefined

[16] University of Alabama at Birmingham,undefined

[17] ILSbio,undefined

[18] LLC,undefined

[19] Indiana University School of Medicine,undefined

[20] Institute of Human Virology,undefined

[21] Institute for Systems Biology,undefined

[22] International Genomics Consortium,undefined

[23] Leidos Biomedical,undefined

[24] Massachusetts General Hospital,undefined

[25] McDonnell Genome Institute at Washington University,undefined

[26] Medical College of Wisconsin,undefined

[27] Medical University of South Carolina,undefined

[28] Memorial Sloan Kettering Cancer Center,undefined

[29] Montefiore Medical Center,undefined

[30] Bronx,undefined

[31] NantOmics,undefined

[32] National Cancer Institute,undefined

[33] National Hospital,undefined

[34] National Human Genome Research Institute,undefined

[35] National Institute of Environmental Health Sciences,undefined

[36] National Institute on Deafness and Other Communication Disorders,undefined

[37] Ontario Tumour Bank,undefined

[38] London Health Sciences Centre,undefined

[39] Ontario Tumour Bank,undefined

[40] Ontario Institute for Cancer Research,undefined

[41] Ontario Tumour Bank,undefined

[42] The Ottawa Hospital,undefined

[43] Oregon Health and Science University,undefined

[44] Penrose-St Francis Health Services,undefined

[45] Samuel Oschin Comprehensive Cancer Institute,undefined

[46] Cedars-Sinai Medical Center,undefined

[47] SRA International,undefined

[48] St Joseph’s Candler Health System,undefined

[49] The Research Institute at Nationwide Children’s Hospital,undefined

[50] The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University,undefined

来源：

Nature | 2017年 / 543卷

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学科分类号：

摘要：

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

引用

页码：378 / 384

页数：6

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