Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

Rheinbay, Esther; Nielsen, Morten Muhlig; Abascal, Federico; Wala, Jeremiah A; Shapira, Ofer; Tiao, Grace; Hornshøj, Henrik; Hess, Julian M; Juul, Randi Istrup; Lin, Ziao; Feuerbach, Lars; Sabarinathan, Radhakrishnan; Madsen, Tobias; Kim, Jaegil; Mularoni, Loris; Shuai, Shimin; Lanzos, Andrés; Herrmann, Carl; Maruvka, Yosef E; Shen, Ciyue; ... (2020). Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature, 578(7793), pp. 102-111. Springer Nature 10.1038/s41586-020-1965-x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Lanzos Camaioni, Andrés Arturo; Carlevaro Fita, Joana; Rubin, Mark Andrew and Johnson, Rory Baldwin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-4687

Publisher:

Springer Nature

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

24 Apr 2020 17:07

Last Modified:

24 Apr 2020 17:16

Publisher DOI:

10.1038/s41586-020-1965-x

PubMed ID:

32025015

BORIS DOI:

10.7892/boris.143031

URI:

https://boris.unibe.ch/id/eprint/143031

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