Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11908
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dc.contributor.authorAnaka, Matthewen
dc.contributor.authorHudson, Christopheren
dc.contributor.authorLo, Pu-Hanen
dc.contributor.authorDo, Hongdoen
dc.contributor.authorCaballero, Otavia Len
dc.contributor.authorDavis, Ian Den
dc.contributor.authorDobrovic, Alexanderen
dc.contributor.authorCebon, Jonathan Sen
dc.contributor.authorBehren, Andreasen
dc.date.accessioned2015-05-16T01:32:26Z
dc.date.available2015-05-16T01:32:26Z
dc.date.issued2013-10-11en
dc.identifier.citationBmc Medical Genomics 2013; 6(): 40en
dc.identifier.govdoc24119551en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/11908en
dc.description.abstractIntratumoral heterogeneity is a major obstacle for the treatment of cancer, as the presence of even minor populations that are insensitive to therapy can lead to disease relapse. Increased clonal diversity has been correlated with a poor prognosis for cancer patients, and we therefore examined genetic, transcriptional, and functional diversity in metastatic melanoma.Amplicon sequencing and SNP microarrays were used to profile somatic mutations and DNA copy number changes in multiple regions from metastatic lesions. Clonal genetic and transcriptional heterogeneity was also assessed in single cell clones from early passage cell lines, which were then subjected to clonogenicity and drug sensitivity assays.MAPK pathway and tumor suppressor mutations were identified in all regions of the melanoma metastases analyzed. In contrast, we identified copy number abnormalities present in only some regions in addition to homogeneously present changes, suggesting ongoing genetic evolution following metastatic spread. Copy number heterogeneity from a tumor was represented in matched cell line clones, which also varied in their clonogenicity and drug sensitivity. Minor clones were identified based on dissimilarity to the parental cell line, and these clones were the most clonogenic and least sensitive to drugs. Finally, treatment of a polyclonal cell line with paclitaxel to enrich for drug-resistant cells resulted in the adoption of a gene expression profile with features of one of the minor clones, supporting the idea that these populations can mediate disease relapse.Our results support the hypothesis that minor clones might have major consequences for patient outcomes in melanoma.en
dc.language.isoenen
dc.subject.otherCell Line, Tumoren
dc.subject.otherClone Cells.pathologyen
dc.subject.otherDNA Copy Number Variationsen
dc.subject.otherFemaleen
dc.subject.otherGenetic Variationen
dc.subject.otherHumansen
dc.subject.otherMaleen
dc.subject.otherMelanoma.genetics.pathologyen
dc.subject.otherNeoplasm Metastasisen
dc.subject.otherOligonucleotide Array Sequence Analysisen
dc.subject.otherPolymorphism, Single Nucleotideen
dc.subject.otherTranscriptomeen
dc.titleIntratumoral genetic heterogeneity in metastatic melanoma is accompanied by variation in malignant behaviors.en
dc.typeJournal Articleen
dc.identifier.journaltitleBMC medical genomicsen
dc.identifier.affiliationjonathan.cebon@ludwig.edu.au.en
dc.identifier.affiliationCancer Immuno-biology Lab, Ludwig Institute for Cancer Research Melbourne, Austin Branch, Melbourne, Victoria 3084, Australiaen
dc.identifier.doi10.1186/1755-8794-6-40en
dc.description.pages40en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/24119551en
dc.type.austinJournal Articleen
local.name.researcherCebon, Jonathan S
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptSurgery (University of Melbourne)-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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