Integrated genomic and molecular characterization of cervical cancer
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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. This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types. Cervical cancer is one of the main causes of cancer-related deaths worldwide, and 95% of cases result from human papilloma virus (HPV) infection. The Cancer Genome Atlas Research Network now reports the genomic and molecular characterization of 228 primary cervical cancers. The authors identify significantly mutated genes and pathways that differ by cervical cancer subtype, and find that keratin-low squamous, keratin-high squamous and adenocarcinoma-rich clusters are marked by different HPV types and molecular features.
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The record
- Venue
- Nature
- Topic
- Cancer-related molecular mechanisms research
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Bank of CanadaBC Cancer AgencyOttawa HospitalCanada's Michael Smith Genome Sciences CentreOntario Institute for Cancer ResearchLondon Health Sciences Centre
- Funders
- National Cancer InstituteNational Human Genome Research InstituteSidney Kimmel Comprehensive Cancer CenterNational Institutes of HealthHospital de Câncer de BarretosBroad InstituteResearch Institute, Nationwide Children's HospitalJohns Hopkins UniversityMemorial Sloan-Kettering Cancer CenterUniversity of South CarolinaBuck Institute for Research on AgingCedars-Sinai Medical CenterMassachusetts Institute of TechnologySchool of Medicine, Indiana UniversityLondon Health Sciences CentreHarvard UniversityUniversity of Texas MD Anderson Cancer CenterBeckman Research Institute, City of HopeUniversitetet i BergenCanada's Michael Smith Genome Sciences CentreSRA InternationalMassachusetts General HospitalLeidosNationwide Children's Hospital
- Keywords
- Cervical cancerAPOBECARID1ACancer researchBiologyKRASCancerPTENAdenocarcinomaCDKN2AGeneOncologyGeneticsMedicineMutationColorectal cancerGenomePI3K/AKT/mTOR pathway
- Has abstract in OpenAlex
- yes