Abstract
Tumorigenesis is a multi-step process, involving the acquisition of multiple oncogenic mutations that transform cells, resulting in systemic dysregulation that enables proliferation, invasion, and other cancer hallmarks. The goal of precision medicine is to identify therapeutically-actionable mutations from large-scale omic datasets. However, the multiplicity of oncogenes required for transformation, known as oncogenic collaboration, makes assigning effective treatments difficult. Motivated by this observation, we propose a new type of oncogenic collaboration where mutations in genes that interact with an oncogene may contribute to the oncogene's deleterious potential, a new genomic feature that we term "surrogate oncogenes." Surrogate oncogenes are representatives of these mutated subnetworks that interact with oncogenes. By mapping mutations to a protein-protein interaction network, we determine the significance of the observed distribution using permutation-based methods. For a panel of 38 breast cancer cell lines, we identified a significant number of surrogate oncogenes in known oncogenes such as BRCA1 and ESR1, lending credence to this approach. In addition, using Random Forest Classifiers, we show that these significant ...Continue Reading
References
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 13, 2006·Cancer Cell·Richard M NeveJoe W Gray
Feb 10, 2009·Clinical Breast Cancer·Philippe L Bedard, Martine J Piccart-Gebhart
Feb 11, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joel S ParkerPhilip S Bernard
Jun 29, 2010·Oncogene·A ChakrabartyC L Arteaga
Oct 5, 2010·Annual Review of Pathology·Gilda da Cunha SantosMing Sound Tsao
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Apr 30, 2011·Genome Biology·Craig H MermelGad Getz
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Aug 13, 2011·Nature·Alice H BergerPier Paolo Pandolfi
Sep 13, 2011·Genome Research·Giovanni CirielloNikolaus Schultz
Oct 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Laura M HeiserPaul T Spellman
Jan 20, 2012·Lancet·José BaselgaUNKNOWN NeoALTTO Study Team
Mar 31, 2012·Nature·Mathew J GarnettCyril H Benes
Jul 5, 2012·Genome Research·Nathan D DeesLi Ding
Sep 25, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Feb 7, 2013·Genome Biology·Ali BashashatiSohrab P Shah
Mar 19, 2013·Current Protocols in Bioinformatics·Giovanni CirielloNikolaus Schultz
May 18, 2013·Seminars in Cancer Biology·Sakshi GulatiPaul A Bates
Jun 19, 2013·Nature·Michael S LawrenceGad Getz
Sep 17, 2013·Nature Methods·Matan HofreeTrey Ideker
Oct 11, 2013·Molecular Cancer Therapeutics·Davide ZecchinFederica Di Nicolantonio
Nov 2, 2013·Genome Biology·Anneleen DaemenJoe W Gray
Jun 2, 2014·Nature Biotechnology·James C CostelloGustavo Stolovitzky