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Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients

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Title: Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients
Authors: Nteliopoulos, G
Page, K
Hills, A
Howarth, K
Emmett, W
Green, E
Martinson, LJ
Fernadez-Garcia, D
Hastings, R
Guttery, DS
Kenny, L
Stebbing, J
Cleator, S
Rehman, F
Gleason, KLT
Sanela, A
Ion, C
Rushton, AJ
Rosenfeld, N
Coombes, RC
Shaw, JA
Item Type: Journal Article
Abstract: Purpose There is growing interest in the application of circulating tumour DNA (ctDNA) as a sensitive tool for monitoring tumour evolution and guiding targeted therapy in patients with cancer. However, robust comparisons of different platform technologies are still required. Here we compared the InVisionSeq™ ctDNA Assay with the Oncomine™ Breast cfDNA Assay to assess their concordance and feasibility for the detection of mutations in plasma at low (< 0.5%) variant allele fraction (VAF). Methods Ninety-six plasma samples from 50 patients with estrogen receptor (ER)-positive metastatic breast cancer (mBC) were profiled using the InVision Assay. Results were compared to the Oncomine assay in 30 samples from 26 patients, where there was sufficient material and variants were covered by both assays. Longitudinal samples were analysed for 8 patients with endocrine resistance. Results We detected alterations in 59/96 samples from 34/50 patients analysed with the InVision assay, most frequently affecting ESR1, PIK3CA and TP53. Complete or partial concordance was found in 28/30 samples analysed by both assays, and VAF values were highly correlated. Excellent concordance was found for most genes, and most discordant calls occurred at VAF < 1%. In longitudinal samples from progressing patients with endocrine resistance, we detected consistent alterations in sequential samples, most commonly in ESR1 and PIK3CA. Conclusion This study shows that both ultra-deep next-generation sequencing (NGS) technologies can detect genomic alternations even at low VAFs in plasma samples of mBC patients. The strong agreement of the technologies indicates sufficient reproducibility for clinical use as prognosic and predictive biomarker.
Issue Date: 7-Jun-2021
Date of Acceptance: 30-Mar-2021
URI: http://hdl.handle.net/10044/1/90039
DOI: 10.1007/s10549-021-06220-9
ISSN: 0167-6806
Publisher: Springer
Start Page: 465
End Page: 176
Journal / Book Title: Breast Cancer Research and Treatment
Volume: 188
Copyright Statement: © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: NIHR-RP-011-053
RDB01 79560
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Metastatic breast cancer
Endocrine therapy resistance
Circulating tumour DNA (ctDNA)
Next-generation sequencing
CELL-FREE DNA
LEADING TECHNOLOGIES
ESR1 MUTATIONS
CTDNA
CFDNA
Circulating tumour DNA (ctDNA)
Endocrine therapy resistance
Metastatic breast cancer
Next-generation sequencing
Biomarkers, Tumor
Breast Neoplasms
Circulating Tumor DNA
Female
High-Throughput Nucleotide Sequencing
Humans
Reproducibility of Results
Science & Technology
Life Sciences & Biomedicine
Oncology
Metastatic breast cancer
Endocrine therapy resistance
Circulating tumour DNA (ctDNA)
Next-generation sequencing
CELL-FREE DNA
LEADING TECHNOLOGIES
ESR1 MUTATIONS
CTDNA
CFDNA
Oncology & Carcinogenesis
1103 Clinical Sciences
1112 Oncology and Carcinogenesis
Publication Status: Published
Online Publication Date: 2021-06-07
Appears in Collections:Department of Immunology and Inflammation
Department of Surgery and Cancer
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons