Integrated genomic and molecular characterization of cervical cancer

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

351 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)378-384
Number of pages7
JournalNature
Volume543
Issue number7645
DOIs
StatePublished - Mar 16 2017

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

The Cancer Genome Atlas Research Network (2017). Integrated genomic and molecular characterization of cervical cancer. Nature, 543(7645), 378-384. https://doi.org/10.1038/nature21386