Noninvasive Detection of HER2 Amplification with Plasma DNA Digital PCR

被引：137

作者：

Gevensleben, Heidrun ^{[1
]}

Garcia-Murillas, Isaac ^{[1
]}

Graeser, Monika K. ^{[1
]}

Schiavon, Gaia ^{[3
]}

Osin, Peter ^{[2
]}

Parton, Marina ^{[3
]}

Smith, Ian E. ^{[3
]}

Ashworth, Alan ^{[1
]}

Turner, Nicholas C. ^{[1
,3
]}

机构：

[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[2] Royal Marsden Hosp, Dept Pathol, London SW3 6JJ, England

[3] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England

来源：

CLINICAL CANCER RESEARCH | 2013年 / 19卷 / 12期

关键词：

METASTATIC BREAST-CANCER; CIRCULATING FREE DNA;

D O I：

10.1158/1078-0432.CCR-12-3768

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Digital PCR is a highly accurate method of determining DNA concentration. We adapted digital PCR to determine the presence of oncogenic amplification through noninvasive analysis of circulating free plasma DNA and exemplify this approach by developing a plasma DNA digital PCR assay for HER2 copy number. Experimental Design: The reference gene for copy number assessment was assessed experimentally and bioinformatically. Chromosome 17 pericentromeric probes were shown to be suboptimal, and EFTUD2 at chromosome position 17q21.31 was selected for analysis. Digital PCR assay parameters were determined on plasma samples from a development cohort of 65 patients and assessed in an independent validation cohort of plasma samples from 58 patients with metastatic breast cancer. The sequential probability ratio test was used to assign the plasma DNA digital PCR test as being HER2-positive or -negative in the validation cohort. Results: In the development cohort, the HER2:EFTUD2 plasma DNA copy number ratio had a receiver operator area under the curve (AUC) = 0.92 [95% confidence interval (CI), 0.86-0.99, P = 0.0003]. In the independent validation cohort, 64% (7 of 11) of patients with HER2-amplified cancers were classified as plasma digital PCR HER2-positive and 94% (44 of 47) of patients with HER2-nonamplified cancers were classified as digital PCR HER2-negative, with a positive and negative predictive value of 70% and 92%, respectively. Conclusion: Analysis of plasma DNA with digital PCR has the potential to screen for the acquisition of HER2 amplification in metastatic breast cancer. This approach could potentially be adapted to the analysis of any locus amplified in cancer. (C)2013 AACR.

引用

页码：3276 / 3284

页数：9

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