{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:59:40Z","timestamp":1772171980928,"version":"3.50.1"},"reference-count":144,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1446406"],"award-info":[{"award-number":["1446406"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1K22CA143148"],"award-info":[{"award-number":["1K22CA143148"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01LM009722 (Subcontract)"],"award-info":[{"award-number":["R01LM009722 (Subcontract)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005428","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T13:28:29Z","timestamp":1492694909000},"page":"e1005428","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples"],"prefix":"10.1371","volume":"13","author":[{"given":"Thomas A.","family":"Peterson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7067-7012","authenticated-orcid":true,"given":"Iris Ivy M.","family":"Gauran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyong","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9132-5040","authenticated-orcid":true,"given":"DoHwan","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-3883","authenticated-orcid":true,"given":"Maricel G.","family":"Kann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1126\/science.1133427","article-title":"The consensus coding sequences of human breast and colorectal cancers","volume":"314","author":"T Sjoblom","year":"2006","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1126\/science.1145720","article-title":"The genomic landscapes of human breast and colorectal cancers","volume":"318","author":"LD Wood","year":"2007","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/nature08645","article-title":"Complex landscapes of somatic rearrangement in human breast cancer genomes","volume":"462","author":"PJ Stephens","year":"2009","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1126\/science.1208130","article-title":"The mutational landscape of head and neck squamous cell carcinoma","volume":"333","author":"N Stransky","year":"2011","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/nrg3539","article-title":"Emerging patterns of somatic mutations in cancer","volume":"14","author":"IR Watson","year":"2013","journal-title":"Nat Rev Genet"},{"key":"ref6","unstructured":"Parmigiani G, Lin J, Boca S, Sjoblom T, Kinzler K, et al. (2007) Statistical methods for the analysis of cancer genome sequencing data."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nature05610","article-title":"Patterns of somatic mutation in human cancer genomes","volume":"446","author":"C Greenman","year":"2007","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/nature07943","article-title":"The cancer genome","volume":"458","author":"MR Stratton","year":"2009","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"D945","DOI":"10.1093\/nar\/gkq929","article-title":"COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer","volume":"39","author":"SA Forbes","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref10","first-page":"baq020","article-title":"GeneCards Version 3: the human gene integrator","author":"M Safran","year":"2010","journal-title":"Database (Oxford)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nrc1299","article-title":"A census of human cancer genes","volume":"4","author":"PA Futreal","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref12","unstructured":"Alliance SS NCI Cancer Gene Index."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: a hub for protein information","volume":"43","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"D992","DOI":"10.1093\/nar\/gkv1123","article-title":"NCG 5.0: updates of a manually curated repository of cancer genes and associated properties from cancer mutational screenings","volume":"44","author":"O An","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"D1023","DOI":"10.1093\/nar\/gkv1268","article-title":"TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes","volume":"44","author":"M Zhao","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e225","DOI":"10.1371\/journal.pcbi.0030225","article-title":"Genetic progression and the waiting time to cancer","volume":"3","author":"N Beerenwinkel","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1158\/0008-5472.CAN-06-1736","article-title":"Distinguishing cancer-associated missense mutations from common polymorphisms","volume":"67","author":"JS Kaminker","year":"2007","journal-title":"Cancer Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1126\/science.1204040","article-title":"Exploring the genomes of cancer cells: progress and promise","volume":"331","author":"MR Stratton","year":"2011","journal-title":"Science"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/nmeth.2410","article-title":"Drilling into big cancer-genome data","volume":"10","author":"V Marx","year":"2013","journal-title":"Nat Methods"},{"key":"ref20","first-page":"pl1","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"J Gao","year":"2013","journal-title":"Sci Signal"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"E Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1101\/gr.5963407","article-title":"Systematic analysis of genetic alterations in tumors using Cancer Genome WorkBench (CGWB)","volume":"17","author":"J Zhang","year":"2007","journal-title":"Genome Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1038\/srep02652","article-title":"Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser","volume":"3","author":"MS Cline","year":"2013","journal-title":"Sci Rep"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nature12213","article-title":"Mutational heterogeneity in cancer and the search for new cancer-associated genes","volume":"499","author":"MS Lawrence","year":"2013","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1126\/science.1235122","article-title":"Cancer genome landscapes","volume":"339","author":"B Vogelstein","year":"2013","journal-title":"Science"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cell.2013.03.002","article-title":"Lessons from the cancer genome","volume":"153","author":"LA Garraway","year":"2013","journal-title":"Cell"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"i237","DOI":"10.1093\/bioinformatics\/btq182","article-title":"Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM","volume":"26","author":"CJ Vaske","year":"2010","journal-title":"Bioinformatics"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"3080","DOI":"10.1039\/c3mb70288j","article-title":"Functional and pathway enrichment analysis for integrated regulatory network of high- and low-metastatic lung cancer","volume":"9","author":"QY Chen","year":"2013","journal-title":"Mol Biosyst"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/ng.3168","article-title":"Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes","volume":"47","author":"MD Leiserson","year":"2015","journal-title":"Nat Genet"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1101\/gr.092833.109","article-title":"Identification of rare cancer driver mutations by network reconstruction","volume":"19","author":"A Torkamani","year":"2009","journal-title":"Genome Res"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"bav032","DOI":"10.1093\/database\/bav032","article-title":"Generating a focused view of disease ontology cancer terms for pan-cancer data integration and analysis","volume":"2015","author":"TJ Wu","year":"2015","journal-title":"Database (Oxford)"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"R53","DOI":"10.1186\/gb-2010-11-5-r53","article-title":"A human functional protein interaction network and its application to cancer data analysis","volume":"11","author":"G Wu","year":"2010","journal-title":"Genome Biol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e1000601","DOI":"10.1371\/journal.pcbi.1000601","article-title":"Human cancer protein-protein interaction network: a structural perspective","volume":"5","author":"G Kar","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"6660","DOI":"10.1158\/0008-5472.CAN-09-1133","article-title":"Cancer-specific high-throughput annotation of somatic mutations: computational prediction of driver missense mutations","volume":"69","author":"H Carter","year":"2009","journal-title":"Cancer Res"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1093\/bioinformatics\/btr629","article-title":"Feature-based classifiers for somatic mutation detection in tumour-normal paired sequencing data","volume":"28","author":"J Ding","year":"2012","journal-title":"Bioinformatics"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.ygeno.2011.06.010","article-title":"A new disease-specific machine learning approach for the prediction of cancer-causing missense variants","volume":"98","author":"E Capriotti","year":"2011","journal-title":"Genomics"},{"issue":"Suppl 4","key":"ref37","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1186\/1471-2164-13-S4-S9","article-title":"Domain landscapes of somatic mutations in cancer","volume":"13","author":"NL Nehrt","year":"2012","journal-title":"BMC Genomics"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e1004147","DOI":"10.1371\/journal.pcbi.1004147","article-title":"Protein domain-level landscape of cancer-type-specific somatic mutations","volume":"11","author":"F Yang","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1126\/science.273.5275.595","article-title":"Mapping the protein universe","volume":"273","author":"L Holm","year":"1996","journal-title":"Science"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/S0022-2836(05)80134-2","article-title":"SCOP: a structural classification of proteins database for the investigation of sequences and structures","volume":"247","author":"AG Murzin","year":"1995","journal-title":"J Mol Biol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"6580","DOI":"10.2741\/3175","article-title":"Understanding eukaryotic linear motifs and their role in cell signaling and regulation","volume":"13","author":"F Diella","year":"2008","journal-title":"Front Biosci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/msb.2009.80","article-title":"Edgetic perturbation models of human inherited disorders","volume":"5","author":"Q Zhong","year":"2009","journal-title":"Mol Syst Biol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1136\/amiajnl-2011-000655","article-title":"Incorporating molecular and functional context into the analysis and prioritization of human variants associated with cancer","volume":"19","author":"TA Peterson","year":"2012","journal-title":"J Am Med Inform Assoc"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1093\/bioinformatics\/btq447","article-title":"DMDM: domain mapping of disease mutations","volume":"26","author":"TA Peterson","year":"2010","journal-title":"Bioinformatics"},{"issue":"Suppl 3","key":"ref45","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1471-2164-14-S3-S5","article-title":"A protein domain-centric approach for the comparative analysis of human and yeast phenotypically relevant mutations","volume":"14","author":"TA Peterson","year":"2013","journal-title":"BMC Genomics"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/humu.21466","article-title":"A new face and new challenges for Online Mendelian Inheritance in Man (OMIM(R))","volume":"32","author":"J Amberger","year":"2011","journal-title":"Hum Mutat"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/nar\/gkg095","article-title":"The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003","volume":"31","author":"B Boeckmann","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/nmeth.2642","article-title":"IntOGen-mutations identifies cancer drivers across tumor types","volume":"10","author":"A Gonzalez-Perez","year":"2013","journal-title":"Nat Methods"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"P Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"IA Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/bioinformatics\/btq330","article-title":"Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor","volume":"26","author":"W McLaren","year":"2010","journal-title":"Bioinformatics"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"e118","DOI":"10.1093\/nar\/gkr407","article-title":"Predicting the functional impact of protein mutations: application to cancer genomics","volume":"39","author":"B Reva","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref53","first-page":"50","article-title":"Mapping the cancer genome. Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies","volume":"296","author":"FS Collins","year":"2007","journal-title":"Sci Am"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"D130","DOI":"10.1093\/nar\/gkr1079","article-title":"NCBI Reference Sequences (RefSeq): current status, new features and genome annotation policy","volume":"40","author":"KD Pruitt","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref55","unstructured":"(2013) UniProtKB\/Swiss-Prot protein knowledgebase release 2013_05 statistics."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"D492","DOI":"10.1093\/nar\/gkp858","article-title":"The NCBI BioSystems database","volume":"38","author":"LY Geer","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"D348","DOI":"10.1093\/nar\/gks1243","article-title":"CDD: conserved domains and protein three-dimensional structure","volume":"41","author":"A Marchler-Bauer","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"D211","DOI":"10.1093\/nar\/gkp985","article-title":"The Pfam protein families database","volume":"38","author":"RD Finn","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S0959-440X(96)80056-X","article-title":"Hidden markov models","volume":"6","author":"SR Eddy","year":"1996","journal-title":"Current opinion in structural biology"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/humu.21194","article-title":"Inferring the functional effects of mutation through clusters of mutations in homologous proteins","volume":"31","author":"P Yue","year":"2010","journal-title":"Hum Mutat"},{"key":"ref61","article-title":"Empirical Null Estimation using Discrete Mixture Distributions and its Application to Protein Domain Data","author":"II Gauran","year":"2016","journal-title":"ArXiv e-prints"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/j.cell.2014.01.051","article-title":"Synonymous mutations frequently act as driver mutations in human cancers","volume":"156","author":"F Supek","year":"2014","journal-title":"Cell"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1111\/pcmr.12413","article-title":"The functional relevance of somatic synonymous mutations in melanoma and other cancers","volume":"28","author":"V Gotea","year":"2015","journal-title":"Pigment Cell Melanoma Res"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"13481","DOI":"10.1073\/pnas.1304227110","article-title":"Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma","volume":"110","author":"JJ Gartner","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1093\/bioinformatics\/17.8.700","article-title":"AL2CO: calculation of positional conservation in a protein sequence alignment","volume":"17","author":"J Pei","year":"2001","journal-title":"Bioinformatics"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"D1049","DOI":"10.1093\/nar\/gku1179","article-title":"Gene Ontology Consortium: going forward","volume":"43","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1745-6150-1-4","article-title":"Mutational hotspots in the TP53 gene and, possibly, other tumor suppressors evolve by positive selection","volume":"1","author":"GV Glazko","year":"2006","journal-title":"Biol Direct"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1073\/pnas.97.7.3352","article-title":"APC mutations in sporadic colorectal tumors: A mutational "hotspot" and interdependence of the "two hits"","volume":"97","author":"AJ Rowan","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nbt.3391","article-title":"Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity","volume":"34","author":"MT Chang","year":"2016","journal-title":"Nat Biotechnol"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1042\/BST20120103","article-title":"Rho family gtpases","volume":"40","author":"A Hall","year":"2012","journal-title":"Biochemical Society Transactions"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"159","DOI":"10.4161\/sgtp.26530","article-title":"Mutationally activated Rho GTPases in cancer","volume":"4","author":"JK Alan","year":"2013","journal-title":"Small GTPases"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"445","DOI":"10.18388\/abp.2004_3583","article-title":"The role of cell adhesion molecule in cancer progression and its application in cancer therapy","volume":"51","author":"T Okegawa","year":"2004","journal-title":"Acta Biochim Pol"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1093\/carcin\/bgu045","article-title":"Cell adhesion molecules and their relation to (cancer) cell stemness","volume":"35","author":"E Farahani","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref74","first-page":"61","article-title":"Holding Tight: Cell Junctions and Cancer Spread","volume":"8","author":"AJ Knights","year":"2012","journal-title":"Trends Cancer Res"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"676731","DOI":"10.1155\/2012\/676731","article-title":"Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins","volume":"2012","author":"G Bendas","year":"2012","journal-title":"Int J Cell Biol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"898","DOI":"10.2741\/3726","article-title":"Tight junctions in cancer metastasis","volume":"16","author":"TA Martin","year":"2011","journal-title":"Front Biosci (Landmark Ed)"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"RA Cairns","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1093\/carcin\/bgt480","article-title":"Cancer as a metabolic disease: implications for novel therapeutics","volume":"35","author":"TN Seyfried","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref79","first-page":"1","article-title":"Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies","volume":"11","author":"LM Phan","year":"2014","journal-title":"Cancer Biol Med"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.2174\/138161209787846711","article-title":"The extracellular matrix regulates cancer progression and therapy response: implications for prognosis and treatment","volume":"15","author":"H Denys","year":"2009","journal-title":"Curr Pharm Des"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1083\/jcb.201102147","article-title":"The extracellular matrix: a dynamic niche in cancer progression","volume":"196","author":"P Lu","year":"2012","journal-title":"J Cell Biol"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1242\/dmm.004077","article-title":"Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer","volume":"4","author":"TR Cox","year":"2011","journal-title":"Dis Model Mech"},{"issue":"Suppl 2","key":"ref83","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.1016\/j.breast.2013.07.012","article-title":"Extracellular matrix components in breast cancer progression and metastasis","volume":"22","author":"T Oskarsson","year":"2013","journal-title":"Breast"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.semcdb.2015.02.010","article-title":"Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes","volume":"40","author":"VR Minciacchi","year":"2015","journal-title":"Semin Cell Dev Biol"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"634865","DOI":"10.1155\/2015\/634865","article-title":"Breast Cancer-Derived Extracellular Vesicles: Characterization and Contribution to the Metastatic Phenotype","volume":"2015","author":"TM Green","year":"2015","journal-title":"Biomed Res Int"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1038\/sj.onc.1207371","article-title":"Ubiquitin and breast cancer","volume":"23","author":"T Ohta","year":"2004","journal-title":"Oncogene"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"4776","DOI":"10.1200\/JCO.2005.05.081","article-title":"The ubiquitin-proteasome pathway and its role in cancer","volume":"23","author":"A Mani","year":"2005","journal-title":"J Clin Oncol"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"298","DOI":"10.2174\/1574891X113089990033","article-title":"The significance of ubiquitin proteasome pathway in cancer development","volume":"8","author":"A Yerlikaya","year":"2013","journal-title":"Recent Pat Anticancer Drug Discov"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/BF00132746","article-title":"The role of proteolytic enzymes in cancer invasion and metastasis","volume":"10","author":"MJ Duffy","year":"1992","journal-title":"Clin Exp Metastasis"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.biochi.2004.10.016","article-title":"Functional imaging of pericellular proteolysis in cancer cell invasion","volume":"87","author":"K Wolf","year":"2005","journal-title":"Biochimie"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1101\/gad.250647.114","article-title":"Pericellular proteolysis in cancer","volume":"28","author":"L Sevenich","year":"2014","journal-title":"Genes Dev"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"e1004176","DOI":"10.1371\/journal.pcbi.1004176","article-title":"Extensive decoupling of metabolic genes in cancer","volume":"11","author":"E Reznik","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"ref93","first-page":"141","article-title":"Metabolic genes in cancer: their roles in tumor progression and clinical implications","volume":"1805","author":"E Furuta","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s10555-008-9166-3","article-title":"The cytoskeleton and cancer","volume":"28","author":"A Hall","year":"2009","journal-title":"Cancer Metastasis Rev"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.bbamcr.2006.07.001","article-title":"Regulation of the actin cytoskeleton in cancer cell migration and invasion","volume":"1773","author":"H Yamaguchi","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"5507","DOI":"10.1111\/bph.12704","article-title":"Movers and shakers: cell cytoskeleton in cancer metastasis","volume":"171","author":"CM Fife","year":"2014","journal-title":"Br J Pharmacol"},{"issue":"Suppl 3","key":"ref97","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1634\/theoncologist.8-suppl_3-5","article-title":"Signal events: Cell signal transduction and its inhibition in cancer","volume":"8","author":"EK Rowinsky","year":"2003","journal-title":"Oncologist"},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006098","article-title":"Signal transduction in cancer","volume":"5","author":"R Sever","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00232-011-9381-7","article-title":"Membrane proteins: the key players of a cancer cell","volume":"242","author":"KR Kampen","year":"2011","journal-title":"J Membr Biol"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1074\/mcp.M800061-MCP200","article-title":"Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry","volume":"8","author":"R Leth-Larsen","year":"2009","journal-title":"Mol Cell Proteomics"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"16218","DOI":"10.1074\/jbc.M109.012096","article-title":"Activation of an olfactory receptor inhibits proliferation of prostate cancer cells","volume":"284","author":"EM Neuhaus","year":"2009","journal-title":"J Biol Chem"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"e85110","DOI":"10.1371\/journal.pone.0085110","article-title":"Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation","volume":"9","author":"G Sanz","year":"2014","journal-title":"PLoS One"},{"key":"ref103","article-title":"Olfactory receptor family receptor, family 7, subfamily C, member 1 is a novel marker of colon cancer-initiating cells and is a potent target of immunotherapy","author":"R Morita","year":"2016","journal-title":"Clin Cancer Res"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1002\/jcb.20600","article-title":"Regulation of human prostate-specific G-protein coupled receptor, PSGR, by two distinct promoters and growth factors","volume":"96","author":"J Weng","year":"2005","journal-title":"J Cell Biochem"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1177\/039463200601900416","article-title":"Prostate\u2014specific G protein couple receptor genes and STAG1\/PMEPA1 in peripheral blood from patients with prostatic cancer","volume":"19","author":"MR Cardillo","year":"2006","journal-title":"Int J Immunopathol Pharmacol"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"15168","DOI":"10.1021\/bi062188q","article-title":"Ankyrin repeat: a unique motif mediating protein-protein interactions","volume":"45","author":"J Li","year":"2006","journal-title":"Biochemistry"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/ng.3002","article-title":"Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer","volume":"46","author":"Y Wang","year":"2014","journal-title":"Nat Genet"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.gde.2010.04.016","article-title":"Rare genetic variants and the risk of cancer","volume":"20","author":"W Bodmer","year":"2010","journal-title":"Curr Opin Genet Dev"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jnutbio.2004.10.010","article-title":"Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells","volume":"16","author":"WK Kim","year":"2005","journal-title":"J Nutr Biochem"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"99ra86","DOI":"10.1126\/scitranslmed.3002442","article-title":"Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab","volume":"3","author":"K Yonesaka","year":"2011","journal-title":"Sci Transl Med"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0065-2423(10)51004-7","article-title":"EGFR and KRAS in colorectal cancer","volume":"51","author":"B Markman","year":"2010","journal-title":"Adv Clin Chem"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/annonc\/mdi057","article-title":"Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives","volume":"16","author":"JP Spano","year":"2005","journal-title":"Ann Oncol"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"5754","DOI":"10.1158\/0008-5472.CAN-13-0576","article-title":"c-Kit is suppressed in human colon cancer tissue and contributes to L1-mediated metastasis","volume":"73","author":"N Gavert","year":"2013","journal-title":"Cancer Res"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1097\/00000478-200312000-00008","article-title":"Analysis of protein expression and gene mutation of c-kit in colorectal neuroendocrine carcinomas","volume":"27","author":"O Akintola-Ogunremi","year":"2003","journal-title":"Am J Surg Pathol"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1097\/DCR.0b013e31823c08b3","article-title":"BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis","volume":"55","author":"MF Kalady","year":"2012","journal-title":"Dis Colon Rectum"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"9","DOI":"10.4137\/BIC.S25248","article-title":"BRAF Mutation in Colorectal Cancer: An Update","volume":"7","author":"D Barras","year":"2015","journal-title":"Biomark Cancer"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.ejca.2015.01.054","article-title":"Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis","volume":"51","author":"F Pietrantonio","year":"2015","journal-title":"Eur J Cancer"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1038\/onc.2012.225","article-title":"RET is a potential tumor suppressor gene in colorectal cancer","volume":"32","author":"Y Luo","year":"2013","journal-title":"Oncogene"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nm.2673","article-title":"Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies","volume":"18","author":"D Lipson","year":"2012","journal-title":"Nat Med"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1002\/ijc.21399","article-title":"Proliferation and Cdk4 expression in microsatellite unstable colon cancers with TGFBR2 mutations","volume":"118","author":"WM Grady","year":"2006","journal-title":"Int J Cancer"},{"key":"ref121","first-page":"846","article-title":"Antisense to CDK4 inhibits the growth of human colon cancer cells HT29","volume":"86","author":"YJ Ye","year":"2006","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.3748\/wjg.v9.i10.2202","article-title":"Expressing patterns of p16 and CDK4 correlated to prognosis in colorectal carcinoma","volume":"9","author":"P Zhao","year":"2003","journal-title":"World J Gastroenterol"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1158\/1541-7786.MCR-13-0479-T","article-title":"ROS1 and ALK fusions in colorectal cancer, with evidence of intratumoral heterogeneity for molecular drivers","volume":"12","author":"DL Aisner","year":"2014","journal-title":"Mol Cancer Res"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1038\/bjc.2013.641","article-title":"ALK gene amplification is associated with poor prognosis in colorectal carcinoma","volume":"109","author":"P Bavi","year":"2013","journal-title":"Br J Cancer"},{"key":"ref125","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1177\/1758834014567117","article-title":"Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract","volume":"7","author":"OB Alese","year":"2015","journal-title":"Ther Adv Med Oncol"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1080\/01635581.2013.795599","article-title":"Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer","volume":"65","author":"ML Slattery","year":"2013","journal-title":"Nutr Cancer"},{"key":"ref127","first-page":"4714","article-title":"Activated Ki-ras enhances sensitivity of ceramide-induced apoptosis without c-Jun NH2-terminal kinase\/stress-activated protein kinase or extracellular signal-regulated kinase activation in human colon cancer cells","volume":"57","author":"M Ohmori","year":"1997","journal-title":"Cancer Res"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/sj.bjc.6601098","article-title":"Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-beta1 integrin complex in colon cancer cells","volume":"89","author":"N Ahmed","year":"2003","journal-title":"Br J Cancer"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/j.1349-7006.2000.tb00958.x","article-title":"Mutation of the SRC gene in endometrial carcinoma","volume":"91","author":"M Sugimura","year":"2000","journal-title":"Jpn J Cancer Res"},{"key":"ref130","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1007\/s10620-008-0519-0","article-title":"Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro","volume":"54","author":"GM Lau","year":"2009","journal-title":"Dig Dis Sci"},{"key":"ref131","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1155\/2011\/946295","article-title":"Crosstalk between activated and inactivated c-Src in hepatocellular carcinoma","volume":"30","author":"ML Chen","year":"2011","journal-title":"Dis Markers"},{"key":"ref132","doi-asserted-by":"publisher","first-page":"6942","DOI":"10.1038\/sj.onc.1206749","article-title":"BRAF and KRAS mutations in stomach cancer","volume":"22","author":"SH Lee","year":"2003","journal-title":"Oncogene"},{"key":"ref133","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/gastro\/got004","article-title":"BRAF mutation in multiple primary cancer with colorectal cancer and stomach cancer","volume":"1","author":"SH Lee","year":"2013","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"ref134","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.jmoldx.2011.03.002","article-title":"KRAS, NRAS, PIK3CA exon 20, and BRAF genotypes in synchronous and metachronous primary colorectal cancers diagnostic and therapeutic implications","volume":"13","author":"K Balschun","year":"2011","journal-title":"J Mol Diagn"},{"key":"ref135","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1093\/neuonc\/not146","article-title":"BRAF-V600E mutation in pediatric and adult glioblastoma","volume":"16","author":"S Dahiya","year":"2014","journal-title":"Neuro Oncol"},{"key":"ref136","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12957-015-0521-x","article-title":"Adult classical glioblastoma with a BRAF V600E mutation","volume":"13","author":"Y Takahashi","year":"2015","journal-title":"World J Surg Oncol"},{"key":"ref137","article-title":"BRAF V600E-mutated diffuse glioma in an adult patient: a case report and review","author":"Y Suzuki","year":"2015","journal-title":"Brain Tumor Pathol"},{"key":"ref138","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1097\/PDM.0b013e31826c7fe0","article-title":"BRAF V600E Mutations in Endometrial Adenocarcinoma","volume":"22","author":"M He","year":"2013","journal-title":"Diagn Mol Pathol"},{"key":"ref139","doi-asserted-by":"publisher","first-page":"6133","DOI":"10.1158\/1078-0432.CCR-04-2670","article-title":"BRAF mutation in endometrial carcinoma and hyperplasia: correlation with KRAS and p53 mutations and mismatch repair protein expression","volume":"11","author":"YZ Feng","year":"2005","journal-title":"Clin Cancer Res"},{"key":"ref140","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/S1995-7645(13)60054-1","article-title":"Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features","volume":"6","author":"M Gao","year":"2013","journal-title":"Asian Pac J Trop Med"},{"key":"ref141","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1097\/PAT.0b013e328344e61b","article-title":"Epidermal growth factor receptor mutation in gastric cancer","volume":"43","author":"Z Liu","year":"2011","journal-title":"Pathology"},{"key":"ref142","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/ajd.12025","article-title":"The epidermal growth factor receptor in squamous cell carcinoma: An emerging drug target","volume":"55","author":"DC Gaffney","year":"2014","journal-title":"Australas J Dermatol"},{"key":"ref143","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1111\/j.1600-0560.2011.01673.x","article-title":"EGFR in melanoma: clinical significance and potential therapeutic target","volume":"38","author":"B Boone","year":"2011","journal-title":"J Cutan Pathol"},{"key":"ref144","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s11523-014-0318-9","article-title":"Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway","volume":"10","author":"A Gross","year":"2015","journal-title":"Target Oncol"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T20:04:33Z","timestamp":1601928273000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005428"}},"subtitle":[],"editor":[{"given":"Marco","family":"Punta","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,4,20]]},"references-count":144,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,4,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005428","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727535204.793531899","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,20]]}}}