
@article {80107,
	title = {Analyses of non-coding somatic drivers in 2,658~cancer whole genomes.},
	journal = {Nature},
	volume = {578},
	year = {2020},
	month = {2020 02},
	pages = {102-111},
	abstract = {<p>The discovery of drivers of cancer has traditionally focused on protein-coding genes. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658\&nbsp;genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers, raise doubts about others and identify novel candidates, including point mutations in the 5{\textquoteright} region of TP53, in the 3{\textquoteright} untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although\&nbsp;point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.</p>
},
	keywords = {Databases, Genetic, DNA Breaks, Gene Expression Regulation, Neoplastic, Genome, Human, Genome-Wide Association Study, Humans, INDEL Mutation, Mutation, Neoplasms},
	issn = {1476-4687},
	doi = {10.1038/s41586-020-1965-x},
	author = {Rheinbay, Esther and Nielsen, Morten Muhlig and Abascal, Federico and Wala, Jeremiah A and Shapira, Ofer and Tiao, Grace and Hornsh{\o}j, Henrik and Hess, Julian M and Juul, Randi Istrup and Lin, Ziao and Feuerbach, Lars and Sabarinathan, Radhakrishnan and Madsen, Tobias and Kim, Jaegil and Mularoni, Loris and Shuai, Shimin and Lanz{\'o}s, Andr{\'e}s and Herrmann, Carl and Maruvka, Yosef E and Shen, Ciyue and Amin, Samirkumar B and Bandopadhayay, Pratiti and Bertl, Johanna and Boroevich, Keith A and Busanovich, John and Carlevaro-Fita, Joana and Chakravarty, Dimple and Chan, Calvin Wing Yiu and Craft, David and Dhingra, Priyanka and Diamanti, Klev and Fonseca, Nuno A and Gonzalez-Perez, Abel and Guo, Qianyun and Hamilton, Mark P and Haradhvala, Nicholas J and Hong, Chen and Isaev, Keren and Johnson, Todd A and Juul, Malene and Kahles, Andre and Kahraman, Abdullah and Kim, Youngwook and Komorowski, Jan and Kumar, Kiran and Kumar, Sushant and Lee, Donghoon and Lehmann, Kjong-Van and Li, Yilong and Liu, Eric Minwei and Lochovsky, Lucas and Park, Keunchil and Pich, Oriol and Roberts, Nicola D and Saksena, Gordon and Schumacher, Steven E and Sidiropoulos, Nikos and Sieverling, Lina and Sinnott-Armstrong, Nasa and Stewart, Chip and Tamborero, David and Tubio, Jose M C and Umer, Husen M and Uusk{\"u}la-Reimand, Liis and Wadelius, Claes and Wadi, Lina and Yao, Xiaotong and Zhang, Cheng-Zhong and Zhang, Jing and Haber, James E and Hobolth, Asger and Imielinski, Marcin and Kellis, Manolis and Lawrence, Michael S and von Mering, Christian and Nakagawa, Hidewaki and Raphael, Benjamin J and Rubin, Mark A and Sander, Chris and Stein, Lincoln D and Stuart, Joshua M and Tsunoda, Tatsuhiko and Wheeler, David A and Johnson, Rory and Reimand, J{\"u}ri and Gerstein, Mark and Khurana, Ekta and Campbell, Peter J and Lopez-Bigas, Nuria and Weischenfeldt, Joachim and Beroukhim, Rameen and Martincorena, I{\~n}igo and Pedersen, Jakob Skou and Getz, Gad}
}
@article {73074,
	title = {The repertoire of mutational signatures in human cancer},
	journal = {Nature},
	volume = {578},
	year = {2020},
	month = {02/2020},
	pages = {94-101},
	abstract = {<p>Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature<sup>1</sup>. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium<sup>2</sup> of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690\&nbsp;somatic mutations from 4,645\&nbsp;whole-genome and 19,184\&nbsp;exome sequences that encompass most types of cancer. We identified 49\&nbsp;single-base-substitution, 11\&nbsp;doublet-base-substitution, 4\&nbsp;clustered-base-substitution and 17\&nbsp;small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses<sup>3-15</sup>, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.</p>
},
	doi = {10.1038/s41586-020-1943-3},
	author = {Alexandrov, Ludmil B and Kim, Jaegil and Haradhvala, Nicholas J and Huang, Mi Ni and Tian Ng, Alvin Wei and Wu, Yang and Boot, Arnoud and Covington, Kyle R and Gordenin, Dmitry A and Bergstrom, Erik N and Islam, S M Ashiqul and Lopez-Bigas, Nuria and Klimczak, Leszek J and McPherson, John R and Morganella, Sandro and Sabarinathan, Radhakrishnan and Wheeler, David A and Mustonen, Ville and Getz, Gad and Rozen, Steven G and Stratton, Michael R and PCAWG}
}
