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A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence.
Canisius, Sander; Martens, John W M; Wessels, Lodewyk F A.
Afiliación
  • Canisius S; Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
  • Martens JW; Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Wessels LF; Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands. l.wessels@nki.nl.
Genome Biol ; 17(1): 261, 2016 12 16.
Article en En | MEDLINE | ID: mdl-27986087
In cancer, mutually exclusive or co-occurring somatic alterations across genes can suggest functional interactions. Existing tests for such patterns make the unrealistic assumption of identical gene alteration probabilities across tumors. We present Discrete Independence Statistic Controlling for Observations with Varying Event Rates (DISCOVER), a novel test that is more sensitive than other methods and controls its false positive rate. A pan-cancer analysis using DISCOVER finds no evidence for widespread co-occurrence, and most co-occurrences previously detected do not exceed expectation by chance. Many mutual exclusivities are identified involving well-known genes related to cell cycle and growth factor signaling, as well as lesser known regulators of Hedgehog signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biología Computacional / Proteínas Hedgehog / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2016 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biología Computacional / Proteínas Hedgehog / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2016 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido