Integrated genomic and molecular characterization of cervical cancer
- PMID: 28112728
- PMCID: PMC5354998
- DOI: 10.1038/nature21386
Integrated genomic and molecular characterization of cervical cancer
Abstract
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.
Conflict of interest statement
There are no competing financial interests.
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Comment in
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Gynaecological cancer: Novel molecular subtypes of cervical cancer - potential clinical consequences.Nat Rev Clin Oncol. 2017 Jul;14(7):397-398. doi: 10.1038/nrclinonc.2017.52. Epub 2017 Apr 11. Nat Rev Clin Oncol. 2017. PMID: 28397825 No abstract available.
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Genomics and 3-Dimensional Brachytherapy for Cervical Cancer: Significant Steps Forward.Int J Radiat Oncol Biol Phys. 2017 Nov 1;99(3):505-509. doi: 10.1016/j.ijrobp.2017.06.2444. Int J Radiat Oncol Biol Phys. 2017. PMID: 29280437 No abstract available.
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