Picoliter-Droplet Digital Polymerase Chain Reaction-Based Analysis of Cell-Free Plasma DNA to Assess EGFR Mutations in Lung Adenocarcinoma That Confer Resistance to Tyrosine-Kinase Inhibitors

The Oncologist
Yoshitaka SekiYuichiro Ohe

Abstract

The objective of this study was to evaluate the utility of analyzing cell-free plasma DNA (cfDNA) by picoliter-droplet digital polymerase chain reaction (ddPCR) to detect EGFR mutations that confer resistance to tyrosine-kinase inhibitors (TKIs) used for treatment of lung adenocarcinoma (LADC). Thirty-five LADC patients who received epidermal growth factor receptor (EGFR)-TKI therapy, including ten who received tumor rebiopsy after development of resistance, were subjected to picoliter-ddPCR-cfDNA analysis to determine the fraction of cfDNA with TKI-sensitive (L858R and inflame exon 19 deletions) and -resistant (i.e., T790M) mutations, as well as their concordance with mutation status in rebiopsied tumor tissues. cfDNA samples from 15 (94%) of 16 patients who acquired resistance were positive for TKI-sensitive mutations. Also, 7 (44%) were positive for the T790M mutation, with fractions of T790M (+) cfDNA ranging from 7.4% to 97%. T790M positivity in cfDNA was consistent in eight of ten patients for whom rebiopsied tumor tissues were analyzed, whereas the remaining cases were negative in cfDNA and positive in rebiopsied tumors. Prior to EGFR-TKI therapy, cfDNAs from 9 (38%) and 0 of 24 patients were positive for TKI-sensitive a...Continue Reading

References

Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tony K F YungY M Dennis Lo
May 28, 2009·Human Mutation·Raquel BlancoMontse Sanchez-Cespedes
Mar 5, 2011·Acta Pharmacologica Sinica·Chao ZhengHong-bin Ji
May 3, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jenn-Yu WuPan-Chyr Yang
May 21, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kenichi SudaTetsuya Mitsudomi
Oct 7, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kazuya TaniguchiKikuya Kato
Apr 19, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kuei-Pin ChungPan-Chyr Yang
Jun 1, 2012·Science Translational Medicine·Tim ForshewNitzan Rosenfeld
Dec 1, 2012·Science Translational Medicine·Rebecca J LearyVictor E Velculescu
Mar 1, 2013·The New England Journal of Medicine·Samuel Aparicio, Carlos Caldas
Mar 9, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Helena A YuGregory J Riely
Jul 10, 2013·Nature Reviews. Clinical Oncology·Emily CrowleyAlberto Bardelli
Oct 9, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Justin F Gainor, Alice T Shaw
Jan 17, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Geoffrey R OxnardPasi A Jänne
Apr 12, 2014·Molecular Cancer Therapeutics·Robert Tjin Tham SjinJuswinder Singh
May 27, 2014·American Society of Clinical Oncology Educational Book·David E GerberDaniel B Costa
Aug 1, 2014·Nature·Ed Yong
Sep 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pierre Laurent-PuigValerie Taly
Oct 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Helena A YuChristine M Lovly
Nov 13, 2014·Clinical Chemistry·Ellen HeitzerJochen B Geigl
Feb 6, 2015·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Fangfei GaoFrank McCaughan
Apr 18, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Masaru WatanabeYasuhiro Koh

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Citations

Jul 31, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·E AlegreA Gonzalez
Nov 7, 2019·Targeted Oncology·Zhengquan YangChunming Ding
Sep 25, 2019·Journal of Personalized Medicine·Andrea Cruz, Weng Kung Peng
Feb 12, 2020·Oncogene·Emmanuelle JeannotCharlotte Proudhon
May 10, 2017·Molecular Diagnosis & Therapy·Susana Olmedillas-LópezDamián García-Olmo
Mar 11, 2017·Surgery Today·Motonobu SaitoTakashi Kohno
May 6, 2020·Cancer Metastasis Reviews·Pieter A BoonstraAnna K L Reyners
Oct 10, 2020·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Xiaojie HuangLiren Ding
Dec 6, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yingyin LiaoAiwu Wu
Jan 29, 2021·Indian Journal of Clinical Biochemistry : IJCB·Jigna JoshiFranky Shah
Mar 28, 2019·Acta Cytologica·Min Huang, Shuanzeng Wei

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