Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance
| Autor: | Ankur Chakravarthy, Ian Reddin, Stephen Henderson, Cindy Dong, Nerissa Kirkwood, Maxmilan Jeyakumar, Daniela Rothschild Rodriguez, Natalia Gonzalez Martinez, Jacqueline McDermott, Xiaoping Su, Nagayasau Egawa, Christina S Fjeldbo, Vilde Eide Skingen, Mari Kyllesø Halle, Camilla Krakstad, Afschin Soleiman, Susanne Sprung, Peter Ellis, Mark Wass, Martin Michaelis, Heidi Lyng, Heidi Fiegl, Helga Salvesen, Gareth Thomas, John Doorbar, Kerry Chester, Andrew Feber, Tim R Fenton |
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| Rok vydání: | 2020 |
| Předmět: |
Cervical cancer
0303 health sciences business.industry medicine.medical_treatment Disease medicine.disease 3. Good health Transcriptome Causes of cancer 03 medical and health sciences 0302 clinical medicine Immune system Immunoediting 030220 oncology & carcinogenesis medicine Cancer research business Adjuvant 030304 developmental biology Epigenomics |
| DOI: | 10.1101/2020.04.02.019711 |
| Popis: | Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell carcinoma (CSCC) to date, totalling 643 tumours and representing patient populations from the USA, Europe and Sub-Saharan Africa, we identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 tumours are largely HPV16-driven, display increased cytotoxic T-lymphocyte infiltration and frequently harbour PIK3CA and EP300 mutations. C2 tumours are associated with shorter overall survival, are frequently driven by HPVs from the HPV18-containing alpha-7 clade, harbour alterations in the Hippo signalling pathway and increased expression of immune checkpoint genes, B7-H3 (also known as CD276) and NT5E (also known as CD73) and PD-L2 (also known as PDCD1LG2). In conclusion, we identify two novel, therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts. |
| Databáze: | OpenAIRE |
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