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dc.contributor.authorBoard, Ruth E
dc.contributor.authorEllison, G
dc.contributor.authorOrr, M C M
dc.contributor.authorKemsley, K R
dc.contributor.authorMcWalter, G
dc.contributor.authorBlockley, L Y
dc.contributor.authorDearden, S P
dc.contributor.authorMorris, C
dc.contributor.authorRanson, Malcolm R
dc.contributor.authorCantarini, M V
dc.contributor.authorDive, Caroline
dc.contributor.authorHughes, A
dc.date.accessioned2010-02-08T16:54:05Z
dc.date.available2010-02-08T16:54:05Z
dc.date.issued2009-11-17
dc.identifier.citationDetection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. 2009, 101 (10):1724-30 Br. J. Canceren
dc.identifier.issn1532-1827
dc.identifier.pmid19861964
dc.identifier.doi10.1038/sj.bjc.6605371
dc.identifier.urihttp://hdl.handle.net/10541/91406
dc.description.abstractBACKGROUND: This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. METHODS: BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. RESULTS: Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. CONCLUSIONS: These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection.
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectCancer DNAen
dc.subjectSkin Canceren
dc.subject.meshAntineoplastic Agents
dc.subject.meshBenzimidazoles
dc.subject.meshCell Line, Tumor
dc.subject.meshDNA Mutational Analysis
dc.subject.meshDNA, Neoplasm
dc.subject.meshDisease-Free Survival
dc.subject.meshHT29 Cells
dc.subject.meshHumans
dc.subject.meshMelanoma
dc.subject.meshMutation
dc.subject.meshPrognosis
dc.subject.meshProto-Oncogene Proteins B-raf
dc.subject.meshSkin Neoplasms
dc.titleDetection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.en
dc.typeArticleen
dc.contributor.departmentAstraZeneca Pharmaceuticals, Alderley Park, Cheshire SK10 4TG, UK.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractBACKGROUND: This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. METHODS: BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. RESULTS: Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. CONCLUSIONS: These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection.


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