@article{1a50d603000841618b563d1fa97645bf,
title = "A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns",
abstract = "In cancer, the primary tumour{\textquoteright}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.",
author = "{PCAWG Tumor Subtypes and Clinical Translation Working Group} and {PCAWG Consortium} and Wei Jiao and Gurnit Atwal and Paz Polak and Rosa Karlic and Edwin Cuppen and Fatima Al-Shahrour and Gurnit Atwal and Bailey, {Peter J.} and Biankin, {Andrew V.} and Boutros, {Paul C.} and Campbell, {Peter J.} and Chang, {David K.} and Cooke, {Susanna L.} and Vikram Deshpande and Faltas, {Bishoy M.} and Faquin, {William C.} and Levi Garraway and Gad Getz and Grimmond, {Sean M.} and Syed Haider and Hoadley, {Katherine A.} and Wei Jiao and Kaiser, {Vera B.} and Rosa Karlic and Mamoru Kato and Kirsten K{\"u}bler and Lazar, {Alexander J.} and Li, {Constance H.} and Louis, {David N.} and Adam Margolin and Sancha Martin and Nahal-Bose, {Hardeep K.} and Nielsen, {G. Petur} and Serena Nik-Zainal and Larsson Omberg and Christine P{\textquoteright}ng and Perry, {Marc D.} and Paz Polak and Esther Rheinbay and Rubin, {Mark A.} and Semple, {Colin A.} and Sgroi, {Dennis C.} and Tatsuhiro Shibata and Reiner Siebert and Jaclyn Smith and Stein, {Lincoln D.} and Stobbe, {Miranda D.} and Sun, {Ren X.} and Shimin Shuai and Wilkerson, {Matthew D.}",
note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-019-13825-8",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",
}