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    Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer.

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    Authors
    Board, Ruth E
    Wardley, Andrew M
    Dixon, J Michael
    Armstrong, Anne C
    Howell, Sacha J
    Renshaw, Lorna
    Donald, Emma
    Greystoke, Alastair
    Ranson, Malcolm R
    Hughes, Andrew
    Dive, Caroline
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    Affiliation
    Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, M20 4BX, UK.
    Issue Date
    2010-04
    
    Metadata
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    Abstract
    Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer. cfDNA extracted (QIAamp Virus spin kit) from blood and matched archival tumour from 46 patients with metastatic breast cancer and 30 patients with localised, operable breast cancer was assessed for hotspot PIK3CA mutations using Amplification Refractory Mutation System (ARMS()) allele-specific PCR and Scorpion probes. PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients. In 41 cases with matched tumour and plasma-derived cfDNA data, concordance (same mutation status in plasma and tumour) was 95%. Where a PIK3CA mutation was present in tumour, the 'pick up' in plasma-derived cfDNA was 80%. PIK3CA mutations were present in tumours from 14/30 (47%) localised breast cancers, but no PIK3CA mutations were detected in matched cfDNA. These data demonstrate feasibility and potential utility of cfDNA for PIK3CA mutation detection in patients with metastatic breast cancer. Studies are underway to qualify PIK3CA mutation in cfDNA as a predictive biomarker allowing patient stratification in clinical trials of mechanism-based therapeutics that target PI3K signalling pathways.
    Citation
    Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer. 2010, 120 (2):461-7 Breast Cancer Res. Treat.
    Journal
    Breast Cancer Research and Treatment
    URI
    http://hdl.handle.net/10541/109320
    DOI
    10.1007/s10549-010-0747-9
    PubMed ID
    20107891
    Type
    Article
    Language
    en
    ISSN
    1573-7217
    ae974a485f413a2113503eed53cd6c53
    10.1007/s10549-010-0747-9
    Scopus Count
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