Integrated genomic and molecular characterization of cervical cancer
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 identifiedSHKBP1,ERBB3,CASP8,HLA-AandTGFBR2as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targetsCD274(also known asPD-L1) andPDCD1LG2(also known asPD-L2), and theBCAR4long 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 ofKRAS,ARID1AandPTENmutations. 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.