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 - Amin, Samirkumar B.
AU - Aminou, Brice
AU - Ammerpohl, Ole
AU - Anderson, Matthew J.
AU - Ang, Yeng
AU - Antonello, Davide
AU - Anur, Pavana
AU - Aparicio, Samuel
AU - Appelbaum, Elizabeth L.
AU - Arai, Yasuhito
AU - Aretz, Axel
AU - Arihiro, Koji
AU - Ariizumi, Shun ichi
AU - Armenia, Joshua
AU - Arnould, Laurent
AU - Asa, Sylvia
AU - Assenov, Yassen
AU - Atwal, Gurnit
AU - Aukema, Sietse
AU - Auman, J. Todd
AU - Aure, Miriam R.R.
AU - Awadalla, Philip
AU - Aymerich, Marta
AU - Bader, Gary D.
AU - Baez-Ortega, Adrian
AU - Bailey, Matthew H.
AU - Bailey, Peter J.
AU - Balasundaram, Miruna
AU - Balu, Saianand
AU - Bandopadhayay, Pratiti
AU - Banks, Rosamonde E.
AU - Barbi, Stefano
AU - Barbour, Andrew P.
AU - Barenboim, Jonathan
AU - Barnholtz-Sloan, Jill
AU - Barr, Hugh
AU - Barrera, Elisabet
AU - Bartlett, John
AU - Bartolome, Javier
AU - Bassi, Claudio
AU - Bathe, Oliver F.
AU - Baumhoer, Daniel
AU - Bavi, Prashant
AU - Baylin, Stephen B.
AU - Bazant, Wojciech
AU - Beardsmore, Duncan
AU - Beck, Timothy A.
AU - Behjati, Sam
AU - Behren, Andreas
AU - Niu, Beifang
AU - Bell, Cindy
AU - Beltran, Sergi
AU - Benz, Christopher
AU - Berchuck, Andrew
AU - Bergmann, Anke K.
AU - Bergstrom, Erik N.
AU - Berman, Benjamin P.
AU - Berney, Daniel M.
AU - Bernhart, Stephan H.
AU - Beroukhim, Rameen
AU - Berrios, Mario
AU - Bersani, Samantha
AU - Bertl, Johanna
AU - Betancourt, Miguel
AU - Bhandari, Vinayak
AU - Bhosle, Shriram G.
AU - Biankin, Andrew V.
AU - Bieg, Matthias
AU - Bigner, Darell
AU - Binder, Hans
AU - Birney, Ewan
AU - Birrer, Michael
AU - Biswas, Nidhan K.
AU - Bjerkehagen, Bodil
AU - Bodenheimer, Tom
AU - Boice, Lori
AU - Bonizzato, Giada
AU - De Bono, Johann S.
AU - Boot, Arnoud
AU - Bootwalla, Moiz S.
AU - Borg, Ake
AU - Borkhardt, Arndt
AU - Boroevich, Keith A.
AU - Borozan, Ivan
AU - Borst, Christoph
AU - Bosenberg, Marcus
AU - Bosio, Mattia
AU - Boultwood, Jacqueline
AU - Bourque, Guillaume
AU - Boutros, Paul C.
AU - Bova, G. Steven
AU - Bowen, David T.
AU - Bowlby, Reanne
AU - Bowtell, David D.L.
AU - Boyault, Sandrine
AU - Boyce, Rich
AU - Boyd, Jeffrey
AU - Brazma, Alvis
AU - Brennan, Paul
AU - Brinkman, Arie B.
AU - Bristow, Robert G.
AU - Broaddus, Russell R.
AU - Brock, Jane E.
AU - Brock, Malcolm
AU - Broeks, Annegien
AU - Brooks, Angela N.
AU - Brooks, Denise
AU - Brors, Benedikt
AU - Brunak, Søren
AU - Bruxner, Timothy J.C.
AU - Bruzos, Alicia L.
AU - Buchanan, Alex
AU - Buchhalter, Ivo
AU - Buchholz, Christiane
AU - Bullman, Susan
AU - Burke, Hazel
AU - Burkhardt, Birgit
AU - Burns, Kathleen H.
AU - Busanovich, John
AU - Bustamante, Carlos D.
AU - Butler, Adam P.
AU - Butte, Atul J.
AU - Byrne, Niall J.
AU - Børresen-Dale, Anne Lise
AU - Caesar-Johnson, Samantha J.
AU - Cafferkey, Andy
AU - Cahill, Declan
AU - Calabrese, Claudia
AU - Caldas, Carlos
AU - Calvo, Fabien
AU - Camacho, Niedzica
AU - Campbell, Peter J.
AU - Campo, Elias
AU - Cantù, Cinzia
AU - Cao, Shaolong
AU - Carey, Thomas E.
AU - Carlevaro-Fita, Joana
AU - Carlsen, Rebecca
AU - Cataldo, Ivana
AU - Cazzola, Mario
AU - Cebon, Jonathan
AU - Cerfolio, Robert
AU - Ding, Li
AU - Fulton, Lucinda A.
AU - Fulton, Robert S.
AU - Govindan, Ramaswamy
AU - Jayasinghe, Reyka
AU - Ley, Tim
AU - Miller, Christopher A.
AU - Mutch, David
AU - Wendl, Michael C.
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
M3 - Article
C2 - 32025001
AN - SCOPUS:85079063026
SN - 1061-4036
VL - 52
SP - 320
EP - 330
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -