@article{8648606,
  abstract     = {{The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 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 drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although 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.}},
  author       = {{Rheinbay, Esther and Nielsen, Morten Muhlig and Abascal, Federico and Wala, Jeremiah A and Shapira, Ofer and Tiao, Grace and Hornshøj, 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 Lanzós, Andrés 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 MC and Umer, Husen M and Uusküla-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, Jüri and Gerstein, Mark and Khurana, Ekta and Campbell, Peter J and López-Bigas, Núria and Weischenfeldt, Joachim and Beroukhim, Rameen and Martincorena, Iñigo and Pedersen, Jakob Skou and Getz, Gad and PCAWG Drivers and Functional Interpretation Working Group, the and Marchal, Kathleen and Pulido-Tamayo, Sergio and Verbeke, Lieven}},
  issn         = {{0028-0836}},
  journal      = {{NATURE}},
  keywords     = {{TERT PROMOTER MUTATIONS,REGULATORY MUTATIONS,RECURRENT,GENES,DISCOVERY,LANDSCAPE,TARGET,ANNOTATION,EXPRESSION,SELECTION}},
  language     = {{eng}},
  number       = {{7793}},
  pages        = {{102--111}},
  title        = {{Analyses of non-coding somatic drivers in 2,658 cancer whole genomes}},
  url          = {{http://doi.org/10.1038/s41586-020-1965-x}},
  volume       = {{578}},
  year         = {{2020}},
}

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