s42003-020-0884-6.pdf (1.72 MB)

DNA copy number motifs are strong and independent predictors of survival in breast cancer.

Download (1.72 MB)
journal contribution
posted on 17.04.2020 by Arne V Pladsen, Gro Nilsen, Oscar M Rueda, Miriam R Aure, Ørnulf Borgan, Knut Liestøl, Valeria Vitelli, Arnoldo Frigessi, Anita Langerød, Anthony Mathelier, OSBREAC, Olav Engebråten, Vessela Kristensen, David C Wedge, Peter Van Loo, Carlos Caldas, Anne-Lise Børresen-Dale, Hege G Russnes, Ole Christian Lingjærde
Somatic copy number alterations are a frequent sign of genome instability in cancer. A precise characterization of the genome architecture would reveal underlying instability mechanisms and provide an instrument for outcome prediction and treatment guidance. Here we show that the local spatial behavior of copy number profiles conveys important information about this architecture. Six filters were defined to characterize regional traits in copy number profiles, and the resulting Copy Aberration Regional Mapping Analysis (CARMA) algorithm was applied to tumors in four breast cancer cohorts (n = 2919). The derived motifs represent a layer of information that complements established molecular classifications of breast cancer. A score reflecting presence or absence of motifs provided a highly significant independent prognostic predictor. Results were consistent between cohorts. The nonsite-specific occurrence of the detected patterns suggests that CARMA captures underlying replication and repair defects and could have a future potential in treatment stratification.

Funding

Crick (Grant ID: 10202, Grant title: Van Loo FC001202)

History

Licence

Exports

Logo branding

Licence

Exports