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    Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.

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    Authors
    Board, Ruth E
    Ellison, G
    Orr, M C M
    Kemsley, K R
    McWalter, G
    Blockley, L Y
    Dearden, S P
    Morris, C
    Ranson, Malcolm R
    Cantarini, M V
    Dive, Caroline
    Hughes, A
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    Affiliation
    AstraZeneca Pharmaceuticals, Alderley Park, Cheshire SK10 4TG, UK.
    Issue Date
    2009-11-17
    
    Metadata
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    Abstract
    BACKGROUND: 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.
    Citation
    Detection 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. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/91406
    DOI
    10.1038/sj.bjc.6605371
    PubMed ID
    19861964
    Type
    Article
    Language
    en
    ISSN
    1532-1827
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.bjc.6605371
    Scopus Count
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research
    Clinical and Experimental Pharmacology Group
    Medical Oncology

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