1. DNA copy number motifs are strong and independent predictors of survival in breast cancer
- Author
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Pladsen, A.V., Nilsen, G., Rueda, O.M., Aure, M.R., Borgan, Ø., Liestøl, K., Vitelli, V., Frigessi, A., Langerød, A., Mathelier, A., Bathen, T.F., Borgen, E., Børresen-Dale, A.-L., Engebråten, O., Fritzman, B., Garred, Ø., Geisler, J., Geitvik, G.A., Hofvind, S., Kristensen, V., Kåresen, R., Lingjærde, O.C., Mælandsmo, G.M., Naume, B., Russnes, H.G., Sahlberg, K.K., Sauer, T., Skjerven, H.K., Schlichting, E., Sørlie, T., Wedge, D.C., Van Loo, P., Caldas, C., Pladsen, Arne V [0000-0001-7765-6823], Rueda, Oscar M [0000-0003-0008-4884], Mathelier, Anthony [0000-0001-5127-5459], Wedge, David C [0000-0002-7572-3196], Van Loo, Peter [0000-0003-0292-1949], Caldas, Carlos [0000-0003-3547-1489], Russnes, Hege G [0000-0001-8724-1891], Lingjærde, Ole Christian [0000-0003-3565-4912], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Genome instability ,Gene Dosage ,Medicine (miscellaneous) ,Tumour biomarkers ,chemistry.chemical_compound ,Breast cancer ,0302 clinical medicine ,Risk Factors ,Databases, Genetic ,Cancer genomics ,Computational models ,lcsh:QH301-705.5 ,Manchester Cancer Research Centre ,food and beverages ,Middle Aged ,Prognosis ,3. Good health ,030220 oncology & carcinogenesis ,Female ,General Agricultural and Biological Sciences ,Algorithms ,DNA Copy Number Variations ,Clinical Decision-Making ,Breast Neoplasms ,Computational biology ,Biology ,Risk Assessment ,Article ,General Biochemistry, Genetics and Molecular Biology ,Genomic Instability ,03 medical and health sciences ,Predictive Value of Tests ,medicine ,Biomarkers, Tumor ,Humans ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Gene Expression Profiling ,fungi ,Cancer ,medicine.disease ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,Spatial behavior ,Personalized medicine ,business ,Outcome prediction ,Transcriptome ,Genome architecture ,DNA - Abstract
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., Pladsen et al. develop Copy Aberration Regional Mapping Analysis (CARMA), an algorithm that derives motifs for copy number profiles in breast cancers by integrating several features, to predict breast cancer prognosis and stratifications. Their algorithm can detect replication and repair defects and can be used in personalized medicine.
- Published
- 2020