TY - JOUR
T1 - The landscape of viral associations in human cancers
AU - PCAWG Pathogens
AU - PCAWG Consortium
AU - Zapatka, Marc
AU - Borozan, Ivan
AU - Brewer, Daniel S.
AU - Iskar, Murat
AU - Grundhoff, Adam
AU - Alawi, Malik
AU - Desai, Nikita
AU - Sültmann, Holger
AU - Moch, Holger
AU - Alawi, Malik
AU - Borozan, Ivan
AU - Cooper, Colin S.
AU - Desai, Nikita
AU - Eils, Roland
AU - Ferretti, Vincent
AU - Grundhoff, Adam
AU - Iskar, Murat
AU - Kleinheinz, Kortine
AU - Lichter, Peter
AU - Nakagawa, Hidewaki
AU - Ojesina, Akinyemi I.
AU - Pedamallu, Chandra Sekhar
AU - Schlesner, Matthias
AU - Su, Xiaoping
AU - Zapatka, Marc
AU - Ferretti, Vincent
AU - Lichter, Peter
AU - Aaltonen, Lauri A.
AU - Abascal, Federico
AU - Abeshouse, Adam
AU - Aburatani, Hiroyuki
AU - Adams, David J.
AU - Agrawal, Nishant
AU - Ahn, Keun Soo
AU - Ahn, Sung Min
AU - Aikata, Hiroshi
AU - Akbani, Rehan
AU - Akdemir, Kadir C.
AU - Al-Ahmadie, Hikmat
AU - Al-Sedairy, Sultan T.
AU - Al-Shahrour, Fatima
AU - Alawi, Malik
AU - Albert, Monique
AU - Aldape, Kenneth
AU - Alexandrov, Ludmil B.
AU - Ally, Adrian
AU - Alsop, Kathryn
AU - Alvarez, Eva G.
AU - Amary, Fernanda
AU - Frenkel-Morgenstern, Milana
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer.
AB - Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer.
UR - http://www.scopus.com/inward/record.url?scp=85079063026&partnerID=8YFLogxK
U2 - 10.1038/s41588-019-0558-9
DO - 10.1038/s41588-019-0558-9
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C2 - 32025001
AN - SCOPUS:85079063026
SN - 1061-4036
VL - 52
SP - 320
EP - 330
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -
