National Institute of Health The Cancer Genome Atlas National Cancer Institute National Human Genome Research Institute
Home > Publications > Integrated genomic and molecular characterization of cervical cancer, 2017

Integrated Genomic and Molecular Characterization of Cervical Cancer

Nature, 23 January 2017

DOI: 10.1038/nature21386

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, the largest comprehensive genomic study of cervical cancer to date. We observed striking APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered novel amplifications in immune targets CD274/PD-L1 and PDCD1LG2/PD-L2, and the BCAR4 lncRNA that has been associated with response to lapatinib. HPV integration was observed in all HPV18-related cases and 76% of HPV16-related cases, 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 tumors with 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.

Supplementary Data Files

Views of the Data

Tools for Exploring Data and Analyses

Associated Data Files

Participant List, Sample List, BAM File List, and Full Listing of TCGA Archives for Data Freeze

Clinical

Mutations

Reverse Phase Protein Array (RPPA) Expression

RNA Expression from IlluminaHiseq RNASeq

SNP and Copy Number variation from Affymetrix SNP6

IlluminaHiSeq Low Pass Whole Genome Sequencing

miRNA from Illumina HiSeq 2000

Methylation from Illumina Infinium Human Methylation450

Additional Information