Oncotarget

Research Papers:

The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M

Jeng-Sen Tseng, Kang-Yi Su, Tsung-Ying Yang, Kun-Chieh Chen, Kuo-Hsuan Hsu, Hsuan-Yu Chen, Chi-Ren Tsai, Sung-Liang Yu and Gee-Chen Chang _

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Oncotarget. 2016; 7:48059-48069. https://doi.org/10.18632/oncotarget.10351

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Abstract

Jeng-Sen Tseng1,2,*, Kang-Yi Su3,4,*, Tsung-Ying Yang1,2, Kun-Chieh Chen1, Kuo-Hsuan Hsu5,6, Hsuan-Yu Chen7,8,9, Chi-Ren Tsai10,11, Sung-Liang Yu3,4,12,13,14, Gee-Chen Chang1,2,15

1Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

3Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan

4Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

5Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan

6Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

7Institute of Statistical Science, Academia Sinica, Taipei, Taiwan

8College of Medicine, National Taiwan University, Taipei, Taiwan

9College of Life Science, National Taiwan University, Taipei, Taiwan

10Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan

11Institute of Molecular Biology, National Chung-Hsing University, Taichung, Taiwan

12Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

13Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan

14Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan

15Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan

*Co-first authors, these authors contributed equally to this work

Correspondence to:

Gee-Chen Chang, email: [email protected]

Sung-Liang Yu, email: [email protected]

Keywords: T790M, epidermal growth factor receptor (EGFR), lung adenocarcinoma, acquired resistance, rebiopsy

Received: April 19, 2016     Accepted: May 29, 2016     Published: June 30, 2016

ABSTRACT

Different growth kinetics occurring between the sensitive and T790M-containing cells may result in the repopulation of tumor cells over time. Little information has yet been uncovered on whether rebiopsy timing influences the T790M detection rate. We enrolled a total of 98 epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients, who had a history of acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) and available rebiopsy tumor specimens for reassessment of EGFR mutations. Rebiopsy was performed at the time of first EGFR-TKI progression in 54 patients (55.1%); for the other 44 patients (44.9%), rebiopsy was done with an interval from first EGFR-TKI progression (median 470.5 days, range 46-1742 days). Our results indicated that rebiopsy timing did not influence the detection rate of T790M and that the mutation could be identified in patients with a long EGFR-TKI-free interval. For patients without suitable lesions for rebiopsy at the time of EGFR-TKI progression, an attempt to rebiopsy should be considered during the subsequent treatment courses.


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