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dc.contributor.authorCampbell, Catarina D.
dc.contributor.authorKehoe, Sarah M.
dc.contributor.authorHatton, Charles
dc.contributor.authorNiu, Lili
dc.contributor.authorYao, Keluo
dc.contributor.authorHanna, Megan
dc.contributor.authorMondal, Chandrani
dc.contributor.authorLuongo, Lauren
dc.contributor.authorBaker, Alissa C.
dc.contributor.authorPhilips, Juliet
dc.contributor.authorGoff, Deborah J.
dc.contributor.authorRubin, Mark A.
dc.contributor.authorCorso, Gianni
dc.contributor.authorRoviello, Franco
dc.contributor.authorMacConaill, Laura Eleanor
dc.contributor.authorBass, Adam Joel
dc.contributor.authorDavis, Matthew J
dc.contributor.authorEmery, Caroline Margaret
dc.contributor.authorFiorentino, Michelangelo
dc.contributor.authorPolyak, Kornelia
dc.contributor.authorChan, Jennifer Ang
dc.contributor.authorWang, Yufang
dc.contributor.authorFletcher, Jonathan A.
dc.contributor.authorSantagata, Sandro
dc.contributor.authorShivdasani, Ramesh Arjun
dc.contributor.authorKieran, Mark W.
dc.contributor.authorLigon, Keith Lloyd
dc.contributor.authorStiles, Charles Dean
dc.contributor.authorHahn, William C.
dc.contributor.authorMeyerson, Matthew Langer
dc.contributor.authorGarraway, Levi Alexander
dc.contributor.authorJones, Chris
dc.date.accessioned2012-02-12T04:37:08Z
dc.date.issued2009
dc.identifier.citationMacConaill, Laura E., Catarina D. Campbell, Sarah M. Kehoe, Adam J. Bass, Charles Hatton, Lili Niu, Matt Davis, et al. 2009. Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 4(11): e7887.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8156565
dc.description.abstractBackground: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi: 10.1371/journal.pone.0007887en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774511/pdf/en_US
dash.licenseLAA
dc.subjectgenetics and genomicsen_US
dc.subjectoncologyen_US
dc.subjectcancer geneticsen_US
dc.subjectpediatric oncologyen_US
dc.titleProfiling Critical Cancer Gene Mutations in Clinical Tumor Samplesen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMacConaill, Laura Eleanor
dc.date.available2012-02-12T04:37:08Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0007887*
dash.authorsorderedfalse
dash.contributor.affiliatedDavis, Matt
dash.contributor.affiliatedFiorentino, Michelangelo
dash.contributor.affiliatedEmery, Caroline Margaret
dash.contributor.affiliatedFletcher, Jonathan
dash.contributor.affiliatedWang, Yufang
dash.contributor.affiliatedChan, Jennifer
dash.contributor.affiliatedKieran, Mark W.
dash.contributor.affiliatedStiles, Charles
dash.contributor.affiliatedMeyerson, Matthew
dash.contributor.affiliatedSantagata, Sandro
dash.contributor.affiliatedLigon, Keith
dash.contributor.affiliatedGarraway, Levi
dash.contributor.affiliatedPolyak, Kornelia
dash.contributor.affiliatedHahn, William
dash.contributor.affiliatedMacConaill, Laura
dash.contributor.affiliatedBass, Adam
dash.contributor.affiliatedShivdasani, Ramesh


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