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dc.contributor.authorGately, Kathyen
dc.contributor.authorRAFEE, SHEREENen
dc.date.accessioned2020-03-22T08:41:14Z
dc.date.available2020-03-22T08:41:14Z
dc.date.issued2020en
dc.date.submitted2020en
dc.identifier.citationToomey S, Carr A, Mezynski MJ, Elamin Y, Rafee S, Cremona M, Morgan C, Madden S, Abdul-Jalil KI, Gately K, Farrelly A, Kay EW, Kennedy S, O'Byrne K, Grogan L, Breathnach O, Morris PG, Eustace AJ, Fay J, Cummins R, O'Grady A, Kalachand R, O'Donovan N, Kelleher F, O'Reilly A, Doherty M, Crown J, Hennessy BT, Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples., Journal of Translational Medicine, 18, 1, 2020, [1-99]en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/91850
dc.descriptionPUBLISHEDen
dc.description.abstractBackground: An increasing number of anti‐cancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Successful use of these therapies is dependent on the presence or absence of somatic mutations within the patient’s tumor that can confer clinical efficacy or drug resistance. Methods: The aim of our study was to determine the type, frequency, overlap and functional proteomic effects of potentially targetable recurrent somatic hotspot mutations in 47 cancer‐related genes in multiple disease sites that could be potential therapeutic targets using currently available agents or agents in clinical development. Results: Using MassArray technology, of the 1300 patient tumors analysed 571 (43.9%) had at least one somatic mutation. Mutations were identified in 30 different genes. KRAS (16.5%), PIK3CA (13.6%) and BRAF (3.8%) were the most frequently mutated genes. Prostate (10.8%) had the lowest number of somatic mutations identified, while no mutations were identified in sarcoma. Ocular melanoma (90.6%), endometrial (72.4%) and colorectal (66.4%) tumors had the highest number of mutations. We noted high concordance between mutations in different parts of the tumor (94%) and matched primary and metastatic samples (90%). KRAS and BRAF mutations were mutually exclusive. Mutation co‐occurrence involved mainly PIK3CA and PTPN11, and PTPN11 and APC. Reverse Phase Protein Array (RPPA) analysis demonstrated that PI3K and MAPK signalling pathways were more altered in tumors with mutations com‐ pared to wild type tumors. Conclusions: Hotspot mutational profiling is a sensitive, high‐throughput approach for identifying mutations of clini‐ cal relevance to molecular based therapeutics for treatment of cancer, and could potentially be of use in identifying novel opportunities for genotype‐driven clinical trials.en
dc.description.sponsorshipThis work was supported by Science Foundation Ireland‐funded Molecular Therapeutics for Cancer Ireland (08‐SRC‐B1410), the Health Research Board (HRA/POR2012/054), the North East Cancer Research and Education Trust (NECRET), and the Fox and Kerins Families.en
dc.format.extent[1-99]en
dc.language.isoenen
dc.relation.ispartofseriesJournal of Translational Medicineen
dc.relation.ispartofseries18en
dc.relation.ispartofseries1en
dc.rightsYen
dc.subjectsomatic mutationsen
dc.subjecttumoursen
dc.subjecttumorsen
dc.subjectcancer treatmenten
dc.titleIdentification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/gatelyken
dc.identifier.peoplefinderurlhttp://people.tcd.ie/rafeesen
dc.identifier.rssinternalid213060en
dc.identifier.doihttp://dx.doi.org/10.1186/s12967-020-02273-4en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber08‐SRC‐B1410en
dc.contributor.sponsorGrantNumberHRA/POR2012/054en
dc.contributor.sponsorGrantNumberNorth East Cancer Research and Education Trust (NECRET)en
dc.relation.doi10.1186/s12967-020-02273-4en
dc.relation.citesCitesen
dc.subject.TCDThemeCanceren
dc.subject.TCDTagPrecision Medicineen
dc.identifier.orcid_id0000-0002-9616-424Xen
dc.subject.darat_thematicHealthen
dc.status.accessibleNen


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