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Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer

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Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer. / Gasch, Christin; Oldopp, Theresa; Mauermann, Oliver; Gorges, Tobias M; Andreas, Antje; Coith, Cornelia; Müller, Volkmar; Fehm, Tanja; Janni, Wolfgang; Pantel, Klaus; Riethdorf, Sabine.

In: MOL ONCOL, Vol. 10, No. 8, 10.2016, p. 1330-43.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gasch, C, Oldopp, T, Mauermann, O, Gorges, TM, Andreas, A, Coith, C, Müller, V, Fehm, T, Janni, W, Pantel, K & Riethdorf, S 2016, 'Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer', MOL ONCOL, vol. 10, no. 8, pp. 1330-43. https://doi.org/10.1016/j.molonc.2016.07.005

APA

Gasch, C., Oldopp, T., Mauermann, O., Gorges, T. M., Andreas, A., Coith, C., Müller, V., Fehm, T., Janni, W., Pantel, K., & Riethdorf, S. (2016). Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer. MOL ONCOL, 10(8), 1330-43. https://doi.org/10.1016/j.molonc.2016.07.005

Vancouver

Gasch C, Oldopp T, Mauermann O, Gorges TM, Andreas A, Coith C et al. Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer. MOL ONCOL. 2016 Oct;10(8):1330-43. https://doi.org/10.1016/j.molonc.2016.07.005

Bibtex

@article{9f3d29a1281546dabb8057f78e28cde4,
title = "Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer",
abstract = "Modern technologies enable detection and characterization of circulating tumor cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as markers for therapeutic response in breast cancer. First studies have incorporated CTC analyses to guide therapeutic interventions and stratification of breast cancer patients. Aim of this study was to analyze characteristic features of CTC as biomarker for predicting resistance to HER2-targeted therapies. Therefore, CTC from metastatic breast cancer patients with HER2-negative primary tumors screened for the prospective randomized phase III trial DETECT III were explored for their HER2 status and the presence of PIK3CA mutations. Detection and characterization of HER2 expression of CTC were conducted with the CellSearch({\textregistered}) system. Fifteen of 179 CTC-positive patients (8.4%) contained ≥1 CTC with strong HER2 expression. Genomic DNA from individual CTC isolated by micromanipulation was propagated by whole genome amplification and analyzed for PIK3CA mutations in exons 9 and 20 by Sanger sequencing. One or more CTC/7.5 mL were detected in 179/290 patients (61.7%). In 109 patients (34.8%), ≥5 CTC/7.5 mL were found. We detected at least one CTC with the mutation p.E542K, p.E545K, p.H1047R, p.H1047L or p.M1043V in 12/33 patients (36.4%). Thirty six of 114 CTC (31.6%) harbored one of these mutations. CTC in individual patients exhibited heterogeneity concerning PIK3CA mutations and HER2 expression. In conclusion, clinically relevant genomic aberrations such as mutations in the hotspot regions of exon 9 and 20 of the PIK3CA gene can be detected in single CTC and might provide insights into mechanisms of resistance to HER2-targeted therapies.",
keywords = "Journal Article",
author = "Christin Gasch and Theresa Oldopp and Oliver Mauermann and Gorges, {Tobias M} and Antje Andreas and Cornelia Coith and Volkmar M{\"u}ller and Tanja Fehm and Wolfgang Janni and Klaus Pantel and Sabine Riethdorf",
note = "Copyright {\textcopyright} 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",
year = "2016",
month = oct,
doi = "10.1016/j.molonc.2016.07.005",
language = "English",
volume = "10",
pages = "1330--43",
journal = "MOL ONCOL",
issn = "1574-7891",
publisher = "Elsevier",
number = "8",

}

RIS

TY - JOUR

T1 - Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer

AU - Gasch, Christin

AU - Oldopp, Theresa

AU - Mauermann, Oliver

AU - Gorges, Tobias M

AU - Andreas, Antje

AU - Coith, Cornelia

AU - Müller, Volkmar

AU - Fehm, Tanja

AU - Janni, Wolfgang

AU - Pantel, Klaus

AU - Riethdorf, Sabine

N1 - Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PY - 2016/10

Y1 - 2016/10

N2 - Modern technologies enable detection and characterization of circulating tumor cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as markers for therapeutic response in breast cancer. First studies have incorporated CTC analyses to guide therapeutic interventions and stratification of breast cancer patients. Aim of this study was to analyze characteristic features of CTC as biomarker for predicting resistance to HER2-targeted therapies. Therefore, CTC from metastatic breast cancer patients with HER2-negative primary tumors screened for the prospective randomized phase III trial DETECT III were explored for their HER2 status and the presence of PIK3CA mutations. Detection and characterization of HER2 expression of CTC were conducted with the CellSearch(®) system. Fifteen of 179 CTC-positive patients (8.4%) contained ≥1 CTC with strong HER2 expression. Genomic DNA from individual CTC isolated by micromanipulation was propagated by whole genome amplification and analyzed for PIK3CA mutations in exons 9 and 20 by Sanger sequencing. One or more CTC/7.5 mL were detected in 179/290 patients (61.7%). In 109 patients (34.8%), ≥5 CTC/7.5 mL were found. We detected at least one CTC with the mutation p.E542K, p.E545K, p.H1047R, p.H1047L or p.M1043V in 12/33 patients (36.4%). Thirty six of 114 CTC (31.6%) harbored one of these mutations. CTC in individual patients exhibited heterogeneity concerning PIK3CA mutations and HER2 expression. In conclusion, clinically relevant genomic aberrations such as mutations in the hotspot regions of exon 9 and 20 of the PIK3CA gene can be detected in single CTC and might provide insights into mechanisms of resistance to HER2-targeted therapies.

AB - Modern technologies enable detection and characterization of circulating tumor cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as markers for therapeutic response in breast cancer. First studies have incorporated CTC analyses to guide therapeutic interventions and stratification of breast cancer patients. Aim of this study was to analyze characteristic features of CTC as biomarker for predicting resistance to HER2-targeted therapies. Therefore, CTC from metastatic breast cancer patients with HER2-negative primary tumors screened for the prospective randomized phase III trial DETECT III were explored for their HER2 status and the presence of PIK3CA mutations. Detection and characterization of HER2 expression of CTC were conducted with the CellSearch(®) system. Fifteen of 179 CTC-positive patients (8.4%) contained ≥1 CTC with strong HER2 expression. Genomic DNA from individual CTC isolated by micromanipulation was propagated by whole genome amplification and analyzed for PIK3CA mutations in exons 9 and 20 by Sanger sequencing. One or more CTC/7.5 mL were detected in 179/290 patients (61.7%). In 109 patients (34.8%), ≥5 CTC/7.5 mL were found. We detected at least one CTC with the mutation p.E542K, p.E545K, p.H1047R, p.H1047L or p.M1043V in 12/33 patients (36.4%). Thirty six of 114 CTC (31.6%) harbored one of these mutations. CTC in individual patients exhibited heterogeneity concerning PIK3CA mutations and HER2 expression. In conclusion, clinically relevant genomic aberrations such as mutations in the hotspot regions of exon 9 and 20 of the PIK3CA gene can be detected in single CTC and might provide insights into mechanisms of resistance to HER2-targeted therapies.

KW - Journal Article

U2 - 10.1016/j.molonc.2016.07.005

DO - 10.1016/j.molonc.2016.07.005

M3 - SCORING: Journal article

C2 - 27491860

VL - 10

SP - 1330

EP - 1343

JO - MOL ONCOL

JF - MOL ONCOL

SN - 1574-7891

IS - 8

ER -