PIK3CA mutation enrichment and quantitation from blood and tissue.
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Date
2020-10-13Author
Keraite, I
Alvarez-Garcia, V
Garcia-Murillas, I
Beaney, M
Turner, NC
Bartos, C
Oikonomidou, O
Kersaudy-Kerhoas, M
Leslie, NR
Type
Journal Article
Metadata
Show full item recordAbstract
PIK3CA is one of the two most frequently mutated genes in breast cancers, occurring in 30-40% of cases. Four frequent 'hotspot' PIK3CA mutations (E542K, E545K, H1047R and H1047L) account for 80-90% of all PIK3CA mutations in human malignancies and represent predictive biomarkers. Here we describe a PIK3CA mutation specific nuclease-based enrichment assay, which combined with a low-cost real-time qPCR detection method, enhances assay detection sensitivity from 5% for E542K and 10% for E545K to 0.6%, and from 5% for H1047R to 0.3%. Moreover, we present a novel flexible prediction method to calculate initial mutant allele frequency in tissue biopsy and blood samples with low mutant fraction. These advancements demonstrated a quick, accurate and simple detection and quantitation of PIK3CA mutations in two breast cancer cohorts (first cohort n = 22, second cohort n = 25). Hence this simple, versatile and informative workflow could be applicable for routine diagnostic testing where quantitative results are essential, e.g. disease monitoring subject to validation in a substantial future study.
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Research team
Molecular Oncology
Language
eng
Date accepted
2020-09-14
License start date
2020-10-13
Citation
Scientific reports, 2020, 10 (1), pp. 17082 - ?
Publisher
NATURE PORTFOLIO