Detection of breast cancer stem cell gene mutations in circulating free DNA during the evolution of metastases
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Limited knowledge exists on the detection of breast cancer stem cell (BCSC)-related mutations in circulating free DNA (cfDNA) from patients with advanced cancers. Identification of new cancer biomarkers may allow for earlier detection of disease progression and treatment strategy modifications.
We conducted a prospective study to determine the feasibility and prognostic utility of droplet digital polymerase chain reaction (ddPCR)-based BCSC gene mutation analysis of cfDNA in patients with breast cancer.
Detection of quantitative BCSC gene mutation in cfDNA by ddPCR mirrors disease progression and thus may represent a valuable and cost-effective measure of tumor burden. We have previously shown that hematological and neurological expressed 1-like (HN1L), ribosomal protein L39 (RPL39), and myeloid leukemia factor 2 (MLF2) are novel targets for BCSC self-renewal, and targeting these genetic alterations could be useful for personalized genomic-based therapy.
BCSC mutation detection in cfDNA may have important implications for diagnosis, prognosis, and serial monitoring.
KeywordsBreast carcinoma Stem cell Mutation Droplet digital polymerase chain reaction Metastasis
Breast cancer stem cell
Circulating free DNA
Droplet digital polymerase chain reaction
Hematological and neurological expressed 1-like
Ribosomal protein L39
Myeloid leukemia factor 2
RNA deep sequencing
Sorting intolerant from tolerant
Human epidermal growth factor receptor 2
Nitric oxide synthase
Any opinions, findings, and conclusions expressed in this materials are those of the author(s) and do not necessarily reflect those of the American Society of Clinical Oncology® or the Conquer Cancer Foundation, or The Breast Cancer Research Foundation. We would like to thank Dr. Ana María González-Angulo from MD Anderson Hospital who identified the samples from GEICAM investigators.
Conceptualization, ZBL, BD, and JCC; Methodology, ZBL, NEE, AKE, BD, HW, and JCC; Investigation, ZBL, DSC, YL, HW, and BD; Formal Analysis, ZBL, NEE, JEE, and BD.; Resources, AKE, HJH, ZMS, JGD, GBM, and JCC; Writing—Original Draft, ZBL; Writing—Review and Editing, ZBL, JGD, DK, BD, and JCC; Supervision, BD and JCC; Funding Acquisition, JCC.
This work was supported by a 2013 Conquer Cancer Foundation of ASCO Long-term International Fellowship (LIFe) in Breast Cancer, supported by The Breast Cancer Research Foundation.
Compliance with ethical standards
Conflict of interests
The authors declare no potential conflicts of interest with the material reported in this manuscript and have no financial relationship with the organization that funded this study. Individual conflict of interest unrelated to the data presented here are listed in the conflict of interest form.
Research involving human participants and informed consent
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board at the Houston Methodist Hospital (IRB protocol numbers 0908-0265, 0811-0147, and 0208-0033) and written informed consent was obtained from all patients before sample and data collection.
This article does not contain any studies with animals performed by any of the authors.
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