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

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...

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Veröffentlicht in:Breast cancer research and treatment 2010-04, Vol.120 (2), p.461-467
Hauptverfasser: Board, Ruth E, Wardley, Andrew M, Dixon, J. Michael, Armstrong, Anne C, Howell, Sacha, Renshaw, Lorna, Donald, Emma, Greystoke, Alastair, Ranson, Malcolm, Hughes, Andrew, Dive, Caroline
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container_end_page 467
container_issue 2
container_start_page 461
container_title Breast cancer research and treatment
container_volume 120
creator Board, Ruth E
Wardley, Andrew M
Dixon, J. Michael
Armstrong, Anne C
Howell, Sacha
Renshaw, Lorna
Donald, Emma
Greystoke, Alastair
Ranson, Malcolm
Hughes, Andrew
Dive, Caroline
description 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.
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Michael</creatorcontrib><creatorcontrib>Armstrong, Anne C</creatorcontrib><creatorcontrib>Howell, Sacha</creatorcontrib><creatorcontrib>Renshaw, Lorna</creatorcontrib><creatorcontrib>Donald, Emma</creatorcontrib><creatorcontrib>Greystoke, Alastair</creatorcontrib><creatorcontrib>Ranson, Malcolm</creatorcontrib><creatorcontrib>Hughes, Andrew</creatorcontrib><creatorcontrib>Dive, Caroline</creatorcontrib><title>Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>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. 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Michael</au><au>Armstrong, Anne C</au><au>Howell, Sacha</au><au>Renshaw, Lorna</au><au>Donald, Emma</au><au>Greystoke, Alastair</au><au>Ranson, Malcolm</au><au>Hughes, Andrew</au><au>Dive, Caroline</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2010-04-01</date><risdate>2010</risdate><volume>120</volume><issue>2</issue><spage>461</spage><epage>467</epage><pages>461-467</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><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.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>20107891</pmid><doi>10.1007/s10549-010-0747-9</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; SpringerNature Journals
subjects Adult
Aged
Biological and medical sciences
Biomarkers
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - genetics
Cancer
Cancer patients
Cancer research
Cancer therapies
Care and treatment
Class I Phosphatidylinositol 3-Kinases
Clinical Trial
Clinical trials
Deoxyribonucleic acid
DNA
DNA - blood
DNA - genetics
DNA Mutational Analysis
Female
Genes
Genetic aspects
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Mutation
Oncology
Phosphatidylinositol 3-Kinases - genetics
Tumors
title Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer
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