Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12186
Full metadata record
DC FieldValueLanguage
dc.contributor.authorMouradov, Dmitri-
dc.contributor.authorSloggett, Clare-
dc.contributor.authorJorissen, Robert N-
dc.contributor.authorLove, Christopher G-
dc.contributor.authorLi, Shan-
dc.contributor.authorBurgess, Antony W-
dc.contributor.authorArango, Diego-
dc.contributor.authorStrausberg, Robert L-
dc.contributor.authorBuchanan, Daniel-
dc.contributor.authorWormald, Samuel-
dc.contributor.authorO'Connor, Liam-
dc.contributor.authorWilding, Jennifer L-
dc.contributor.authorBicknell, David-
dc.contributor.authorTomlinson, Ian P M-
dc.contributor.authorBodmer, Walter F-
dc.contributor.authorMariadason, John M-
dc.contributor.authorSieber, Oliver M-
dc.date.accessioned2015-05-16T01:50:25Z
dc.date.available2015-05-16T01:50:25Z
dc.date.issued2014-04-22-
dc.identifier.citationCancer Research 2014; 74(12): 3238-47en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12186en
dc.description.abstractHuman colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas. Notably, we found that exome mutation and DNA copy-number spectra in colorectal cancer cell lines closely resembled those seen in primary colorectal tumors. Similarities included the presence of two hypermutation phenotypes, as defined by signatures for defective DNA mismatch repair and DNA polymerase ε proofreading deficiency, along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGFβ, and p53 pathways. Furthermore, we documented mutations enriched in genes involved in chromatin remodeling (ARID1A, CHD6, and SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, and TRRAP). Chromosomal instability was prevalent in nonhypermutated cases, with similar patterns of chromosomal gains and losses. Although paired cell lines derived from the same tumor exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differences mainly reflected a preexisting heterogeneity in the tumor cells. In conclusion, our results establish that human colorectal cancer lines are representative of the main subtypes of primary tumors at the genomic level, further validating their utility as tools to investigate colorectal cancer biology and drug responses.en
dc.language.isoenen
dc.subject.otherCell Line, Tumoren
dc.subject.otherChromosome Aberrationsen
dc.subject.otherColorectal Neoplasms.genetics.metabolismen
dc.subject.otherDNA Copy Number Variationsen
dc.subject.otherDNA Mutational Analysisen
dc.subject.otherExomeen
dc.subject.otherGene Dosageen
dc.subject.otherGene Frequencyen
dc.subject.otherGenes, Neoplasmen
dc.subject.otherHumansen
dc.subject.otherMicrosatellite Instabilityen
dc.subject.otherTranscriptomeen
dc.titleColorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer.en
dc.typeJournal Articleen
dc.identifier.journaltitleCancer researchen
dc.identifier.affiliationCancer and Population Studiesen
dc.identifier.affiliationGroup of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spainen
dc.identifier.affiliationAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, Victoria, Australiaen
dc.identifier.affiliationLudwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, Victoria, Australiaen
dc.identifier.affiliationCancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australiaen
dc.identifier.affiliationLudwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom John.Mariadason@ludwig.edu.au Oliver.Sieber@wehi.edu.au.en
dc.identifier.affiliationLudwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.en
dc.identifier.doi10.1158/0008-5472.CAN-14-0013en
dc.description.pages3238-47en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/24755471en
dc.type.contentTexten
dc.type.austinJournal Articleen
local.name.researcherMariadason, John M
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

34
checked on Mar 28, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.