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dc.contributor.authorChoy, Edwinen_US
dc.contributor.authorMacConaill, Laura E.en_US
dc.contributor.authorCote, Gregory M.en_US
dc.contributor.authorLe, Long P.en_US
dc.contributor.authorShen, Jacson K.en_US
dc.contributor.authorNielsen, Gunnlaugur P.en_US
dc.contributor.authorIafrate, Anthony J.en_US
dc.contributor.authorGarraway, Levi A.en_US
dc.contributor.authorHornicek, Francis J.en_US
dc.contributor.authorDuan, Zhenfengen_US
dc.date.accessioned2014-08-13T14:00:27Z
dc.date.issued2014en_US
dc.identifier.citationChoy, Edwin, Laura E. MacConaill, Gregory M. Cote, Long P. Le, Jacson K. Shen, Gunnlaugur P. Nielsen, Anthony J. Iafrate, Levi A. Garraway, Francis J. Hornicek, and Zhenfeng Duan. 2014. “Genotyping Cancer-Associated Genes in Chordoma Identifies Mutations in Oncogenes and Areas of Chromosomal Loss Involving CDKN2A, PTEN, and SMARCB1.” PLoS ONE 9 (7): e101283. doi:10.1371/journal.pone.0101283. http://dx.doi.org/10.1371/journal.pone.0101283.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12717611
dc.description.abstractThe molecular mechanisms underlying chordoma pathogenesis are unknown. We therefore sought to identify novel mutations to better understand chordoma biology and to potentially identify therapeutic targets. Given the relatively high costs of whole genome sequencing, we performed a focused genetic analysis using matrix-assisted laser desorption/ionization-time of flight mass spectrometer (Sequenom iPLEX genotyping). We tested 865 hotspot mutations in 111 oncogenes and selected tumor suppressor genes (OncoMap v. 3.0) of 45 human chordoma tumor samples. Of the analyzed samples, seven were identified with at least one mutation. Six of these were from fresh frozen samples, and one was from a paraffin embedded sample. These observations were validated using an independent platform using homogeneous mass extend MALDI-TOF (Sequenom hME Genotyping). These genetic alterations include: ALK (A877S), CTNNB1 (T41A), NRAS (Q61R), PIK3CA (E545K), PTEN (R130), CDKN2A (R58*), and SMARCB1 (R40*). This study reports on the largest comprehensive mutational analysis of chordomas performed to date. To focus on mutations that have the greatest chance of clinical relevance, we tested only oncogenes and tumor suppressor genes that have been previously implicated in the tumorigenesis of more common malignancies. We identified rare genetic changes that may have functional significance to the underlying biology and potential therapeutics for chordomas. Mutations in CDKN2A and PTEN occurred in areas of chromosomal copy loss. When this data is paired with the studies showing 18 of 21 chordoma samples displaying copy loss at the locus for CDKN2A, 17 of 21 chordoma samples displaying copy loss at PTEN, and 3 of 4 chordoma samples displaying deletion at the SMARCB1 locus, we can infer that a loss of heterozygosity at these three loci may play a significant role in chordoma pathogenesis.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0101283en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077728/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectGeneticsen
dc.subjectCancer Geneticsen
dc.subjectHuman Geneticsen
dc.subjectMedicine and Health Sciencesen
dc.subjectClinical Geneticsen
dc.subjectPersonalized Medicineen
dc.subjectNeurologyen
dc.subjectNeurological Tumorsen
dc.subjectSpinal Cord Tumorsen
dc.subjectOncologyen
dc.subjectCancers and Neoplasmsen
dc.subjectSarcomasen
dc.subjectBasic Cancer Researchen
dc.titleGenotyping Cancer-Associated Genes in Chordoma Identifies Mutations in Oncogenes and Areas of Chromosomal Loss Involving CDKN2A, PTEN, and SMARCB1en
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorChoy, Edwinen_US
dc.date.available2014-08-13T14:00:27Z
dc.identifier.doi10.1371/journal.pone.0101283*
dash.contributor.affiliatedNielsen, Gunnlaugur
dash.contributor.affiliatedCote, Gregory
dash.contributor.affiliatedChoy, Edwin
dash.contributor.affiliatedMacConaill, Laura
dash.contributor.affiliatedIafrate, Anthony
dash.contributor.affiliatedHornicek, Francis
dash.contributor.affiliatedGarraway, Levi


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