title: Insights into cancer severity from biomolecular interaction mechanisms.
abstract: To attain a deeper understanding of diseases like cancer, it is critical to couple genetics with biomolecular mechanisms. High-throughput sequencing has identified thousands of somatic mutations across dozens of cancers, and there is a pressing need to identify the few that are pathologically relevant. Here we use protein structure and interaction data to interrogate nonsynonymous somatic cancer mutations, identifying a set of 213 molecular interfaces (protein-protein, -small molecule or -nucleic acid) most often perturbed in cancer, highlighting several potentially novel cancer genes. Over half of these interfaces involve protein-small-molecule interactions highlighting their overall importance in cancer. We found distinct differences in the predominance of perturbed interfaces between cancers and histological subtypes and presence or absence of certain interfaces appears to correlate with cancer severity.
authors.affiliation: CellNetworks, Bioquant, Im Neuenheimer Feld 267, University of Heidelberg, 69120 Heidelberg, Germany.|Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Francesco
authors.initials: F
authors.lastname: Raimondi
authors.affiliation: CellNetworks, Bioquant, Im Neuenheimer Feld 267, University of Heidelberg, 69120 Heidelberg, Germany.|Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Gurdeep
authors.initials: G
authors.lastname: Singh
authors.affiliation: CellNetworks, Bioquant, Im Neuenheimer Feld 267, University of Heidelberg, 69120 Heidelberg, Germany.|Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Betts
authors.affiliation: CellNetworks, Bioquant, Im Neuenheimer Feld 267, University of Heidelberg, 69120 Heidelberg, Germany.|Cambridge Cell Networks, St. John's Innovation Centre, Cowley Road, Cambridge CB4 0WS, UK.
authors.forename: Gordana
authors.initials: G
authors.lastname: Apic
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna and Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, 40138 Bologna, Italy.
authors.forename: Ranka
authors.initials: R
authors.lastname: Vukotic
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna and Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, 40138 Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Lincoln
authors.initials: L
authors.lastname: Stein
authors.affiliation: CellNetworks, Bioquant, Im Neuenheimer Feld 267, University of Heidelberg, 69120 Heidelberg, Germany.|Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Russell
mesh_terms: D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins