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

2.50
Hdl Handle:
http://hdl.handle.net/10541/91406
Title:
Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.
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 ( 0000-0002-1726-8850 ) ; Hughes, A
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.
Affiliation:
AstraZeneca Pharmaceuticals, Alderley Park, Cheshire SK10 4TG, UK.
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
Issue Date:
17-Nov-2009
URI:
http://hdl.handle.net/10541/91406
DOI:
10.1038/sj.bjc.6605371
PubMed ID:
19861964
Type:
Article
Language:
en
ISSN:
1532-1827
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research; Clinical and Experimental Pharmacology Group; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorBoard, Ruth Een
dc.contributor.authorEllison, Gen
dc.contributor.authorOrr, M C Men
dc.contributor.authorKemsley, K Ren
dc.contributor.authorMcWalter, Gen
dc.contributor.authorBlockley, L Yen
dc.contributor.authorDearden, S Pen
dc.contributor.authorMorris, Cen
dc.contributor.authorRanson, Malcolm Ren
dc.contributor.authorCantarini, M Ven
dc.contributor.authorDive, Carolineen
dc.contributor.authorHughes, Aen
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.en
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

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