Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study

Marzena Anna Lewandowska; Ewelina Nalejska; Łukasz Żołna; Aleksandra Chrząstek; Bogdan Żurawski; Magdalena Wiśniewska; Manuela Las-Jankowska; Krzysztof Roszkowski; Janusz Kowalewski

doi:10.5114/wo.2019.85879

eISSN: 1897-4309
ISSN: 1428-2526

Contemporary Oncology/Współczesna Onkologia

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2/2019
vol. 23

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abstract:

Original paper

Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study

Marzena Anna Lewandowska

^{1, 2}

,

Ewelina Nalejska

^{1, 2}

,

Łukasz Żołna

²

,

Aleksandra Chrząstek

²

,

Bogdan Żurawski

³

,

Magdalena Wiśniewska

⁴

,

Manuela Las-Jankowska

^{5, 6}

,

Krzysztof Roszkowski

⁷

,

Janusz Kowalewski

²

Department of Molecular Oncology and Genetics, Innovative Medical Forum, Professor Franciszek Lukaszczyk Oncology Centre, Bydgoszcz, Poland
Department of Thoracic Surgery and Tumours, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Centre, Bydgoszcz, Poland
Department of Oncology and Brachytherapy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
Department of Surgical Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
Department of Clinical Oncology, Professor Franciszek Lukaszczyk Oncology Centre, Bydgoszcz, Poland
Department of Oncology, Radiotherapy and Oncological Gynecology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland

Contemp Oncol (Pozn) 2019; 23 (2): 87-91

DOI: https://doi.org/10.5114/wo.2019.85879

Online publish date: 2019/06/13

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AMA

Lewandowska M, Nalejska E, Żołna Ł, et al. Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study. Contemporary Oncology/Współczesna Onkologia. 2019;23(2):87-91. doi:10.5114/wo.2019.85879.

APA

Lewandowska, M., Nalejska, E., Żołna, Ł., Chrząstek, A., Żurawski, B.,  & Wiśniewska, M. et al. (2019). Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study. Contemporary Oncology/Współczesna Onkologia, 23(2), 87-91. https://doi.org/10.5114/wo.2019.85879

Chicago

Lewandowska, Marzena Anna, Ewelina Nalejska, Łukasz Żołna, Aleksandra Chrząstek, Bogdan Żurawski, Magdalena Wiśniewska,  and Manuela Las-Jankowska et al. 2019. "Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study". Contemporary Oncology/Współczesna Onkologia 23 (2): 87-91. doi:10.5114/wo.2019.85879.

Harvard

Lewandowska, M., Nalejska, E., Żołna, Ł., Chrząstek, A., Żurawski, B., Wiśniewska, M., Las-Jankowska, M., Roszkowski, K.,  and Kowalewski, J. (2019). Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study. Contemporary Oncology/Współczesna Onkologia, 23(2), pp.87-91. https://doi.org/10.5114/wo.2019.85879

MLA

Lewandowska, Marzena Anna et al. "Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study." Contemporary Oncology/Współczesna Onkologia, vol. 23, no. 2, 2019, pp. 87-91. doi:10.5114/wo.2019.85879.

Vancouver

Lewandowska M, Nalejska E, Żołna Ł, Chrząstek A, Żurawski B, Wiśniewska M et al. Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study. Contemporary Oncology/Współczesna Onkologia. 2019;23(2):87-91. doi:10.5114/wo.2019.85879.

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Aim of the study
The main purpose of this study was to assess detection of mutations in the epidermal growth factor receptor (EGFR) gene in circulating tumor DNA (ctDNA) as a tool for EGFR tyrosine kinase inhibitor (TKI) monitoring therapy.

Material and methods
The study was conducted using 20 samples from 7 adenocarcinoma patients treated with TKIs. Blood samples for ctDNA analysis were collected in 2015–2016. ctDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (Qiagen) and analyzed using the ctEGFR Mutation Detection Kit (EntroGen).

Results
The most common exon 19 deletion and p.Leu858Arg mutation in exon 21 of the EGFR gene were detected. We observed a correlation between stabilization of patient condition and the lack of p.Thr790Met mutation detection in ctEGFR during TKI treatment (2 out of 7 patients). We also observed a correlation between progression of the disease and p.Thr790Met mutation detection in ctEGFR (3 out of 7 cases). We did not detect ctDNA p.Thr790Metp in two patients in whom progression occurred shortly thereafter. Last but not least, we noticed that good organization during plasma collection and transportation (average time of 6 minutes and 30 seconds) allows to use K2EDTA tubes.

Conclusions
When tissue is limited or insufficient, analysis of the ctEGFR mutational status can be considered as an alternative tool for qualifying patients with non-small cell lung cancer (NSCLC) for TKI therapy, also as a potential monitoring tool. The plasma p.Thr790Met-negative result needs to be verified for the presence of p.Thr790Met-positive tumor tissue.

keywords:

Detection of somatic mutations in ctDNA derived from adenocarcinoma patients – EGFR tyrosine kinase inhibitor monitoring preliminary study

Marzena Anna Lewandowska 1, 2 , Ewelina Nalejska 1, 2 , Łukasz Żołna 2 , Aleksandra Chrząstek 2 , Bogdan Żurawski 3 , Magdalena Wiśniewska 4 , Manuela Las-Jankowska 5, 6 , Krzysztof Roszkowski 7 , Janusz Kowalewski 2

liquid biopsy monitoring, ctDNA, ctEGFR, EGFR c2369C>T (pThr790Met), predictive biomarker, NSCLC, adenocarcinoma

Marzena Anna Lewandowska

^{1, 2}

,

Ewelina Nalejska

^{1, 2}

,

Łukasz Żołna

²

,

Aleksandra Chrząstek

²

,

Bogdan Żurawski

³

,

Magdalena Wiśniewska

⁴

,

Manuela Las-Jankowska

^{5, 6}

,

Krzysztof Roszkowski

⁷

,

Janusz Kowalewski

²