A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
Creators: name: Jiao, Wei
name: Atwal, Gurnit
name: Polak, Paz
name: Karlic, Rosa
name: Cuppen, Edwin
name: Al-Shahrour, Fatima
name: Bailey, Peter J
name: Biankin, Andrew V
name: Boutros, Paul C
name: Campbell, Peter J
name: Chang, David K
name: Cooke, Susanna L
name: Deshpande, Vikram
name: Faltas, Bishoy M
name: Faquin, William C
name: Garraway, Levi
name: Getz, Gad
name: Grimmond, Sean M
name: Haider, Syed
name: Hoadley, Katherine A
name: Kaiser, Vera B
name: Kato, Mamoru
name: Kübler, Kirsten
name: Lazar, Alexander J
name: Li, Constance H
name: Louis, David N
name: Margolin, Adam
name: Martin, Sancha
name: Nahal-Bose, Hardeep K
name: Nielsen, G Petur
name: Nik-Zainal, Serena
name: Omberg, Larsson
name: P’ng, Christine
name: Perry, Marc D
name: Rheinbay, Esther
name: Rubin, Mark A
name: Semple, Colin A
name: Sgroi, Dennis C
name: Shibata, Tatsuhiro
name: Siebert, Reiner
name: Smith, Jaclyn
name: Stein, Lincoln D
name: Stobbe, Miranda D
name: Sun, Ren X
name: Thai, Kevin
name: Wright, Derek W
name: Wu, Chin-Lee
name: Yuan, Ke
name: Zhang, Junjun
name: Danyi, Alexandra
name: de Ridder, Jeroen
name: van Herpen, Carla
name: Lolkema, Martijn P
name: Steeghs, Neeltje
name: Morris, Quaid D
name: Aaltonen, Lauri A
name: Abascal, Federico
name: Abeshouse, Adam
name: Aburatani, Hiroyuki
name: Adams, David J
name: Agrawal, Nishant
name: Ahn, Keun Soo
name: Ahn, Sung-Min
name: Aikata, Hiroshi
name: Akbani, Rehan
name: Akdemir, Kadir C
name: Al-Ahmadie, Hikmat
name: Al-Sedairy, Sultan T
name: Alawi, Malik
name: Albert, Monique
name: Aldape, Kenneth
name: Alexandrov, Ludmil B
name: Ally, Adrian
name: Alsop, Kathryn
name: Alvarez, Eva G
name: Amary, Fernanda
name: Amin, Samirkumar B
name: Aminou, Brice
name: Ammerpohl, Ole
name: Anderson, Matthew J
name: Ang, Yeng
name: Antonello, Davide
name: Anur, Pavana
name: Aparicio, Samuel
name: Appelbaum, Elizabeth L
name: Arai, Yasuhito
name: Aretz, Axel
name: Arihiro, Koji
name: Ariizumi, Shun-ichi
name: Armenia, Joshua
name: Arnould, Laurent
name: Asa, Sylvia
name: Assenov, Yassen
name: Aukema, Sietse
name: Auman, J Todd
name: Aure, Miriam RR
name: Awadalla, Philip
name: Aymerich, Marta
name: Bader, Gary D
name: Baez-Ortega, Adrian
name: Bailey, Matthew H
name: Balasundaram, Miruna
name: Balu, Saianand
name: Bandopadhayay, Pratiti
name: Banks, Rosamonde E
name: Barbi, Stefano
name: Barbour, Andrew P
name: Barenboim, Jonathan
name: Barnholtz-Sloan, Jill
name: Barr, Hugh
name: Barrera, Elisabet
name: Bartlett, John
name: Bartolome, Javier
name: Bassi, Claudio
name: Bathe, Oliver F
name: Baumhoer, Daniel
name: Bavi, Prashant
name: Baylin, Stephen B
name: Bazant, Wojciech
name: Beardsmore, Duncan
name: Beck, Timothy A
name: Behjati, Sam
name: Behren, Andreas
name: Niu, Beifang
name: Bell, Cindy
name: Beltran, Sergi
name: Benz, Christopher
name: Berchuck, Andrew
name: Bergmann, Anke K
name: Bergstrom, Erik N
name: Berman, Benjamin P
name: Berney, Daniel M
name: Bernhart, Stephan H
name: Beroukhim, Rameen
name: Berrios, Mario
name: Bersani, Samantha
name: Bertl, Johanna
name: Betancourt, Miguel
name: Bhandari, Vinayak
name: Bhosle, Shriram G
name: Bieg, Matthias
name: Bigner, Darell
name: Binder, Hans
name: Birney, Ewan
name: Birrer, Michael
name: Biswas, Nidhan K
name: Bjerkehagen, Bodil
name: Bodenheimer, Tom
name: Boice, Lori
name: Bonizzato, Giada
name: De Bono, Johann S
name: Boot, Arnoud
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name: Borg, Ake
name: Borkhardt, Arndt
name: Boroevich, Keith A
name: Borozan, Ivan
name: Borst, Christoph
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name: Broaddus, Russell R
name: Brock, Jane E
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name: Zhang, Xuanping
name: Zhang, Yan
name: Zhang, Zemin
name: Zhao, Zhongming
name: Zheng, Liangtao
name: Zheng, Xiuqing
name: Zhou, Wanding
name: Zhou, Yong
name: Zhu, Bin
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name: Zhu, Jingchun
name: Zhu, Shida
name: Zou, Lihua
name: Zou, Xueqing
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Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology

description: In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.