Balkan Journal of Medical Genetics

DROPLET DIGITAL PCR AS A MOLECULAR TOOL FOR THE DETECTION OF THE EGFR T790M MUTATION IN NSCLC PATIENTS WITH THE EGFR ACTIVATING MUTATIONS
Durgut S, Salihefendić L, Pećar D, Čeko I, Mulahuseinović N, Izmirlija M, Konjhodžić R
*Corresponding Author: Selma Durgut, MD, ALEA Genetic Center, Olovska 67, 71000 Sarajevo, Bosnia and Herzegovina; Mob.: +38761904549, Email: selma.durgut@agc.ba
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DISCUSSION

The main objective of this type of study is to improve the approach to treating oncology patients by providing individualized and accessible therapy. When one considers that around 50% of NSCLC patients experience disease relapse during TKI-targeted therapy and eventually ac- quire the T790M mutation, it becomes crucial to quickly discover molecular resistance mechanisms [20] . In current practice, the preferred method for monitoring resistance mechanisms is to perform a tissue re-biopsy. However, with the development of highly sensitive and reliable mo- lecular technologies, such as ddPCR, analysis can be per- formed from other, minimally invasive types of samples [21] . Our study indicates that the sampling of patients can be significantly facilitated in order to monitor T790M status. Some studies estimate that up to 40% of relapsed NSCLC cases, cannot undergo molecular analysis due to issues with tumor tissue biopsies [22,23] . Two main factors contribute to this problem. Firstly, it is often challenging to obtain sufficient tissue material. As a result, clinicians use a well-known phrase “Tissue is an issue”, since the patient’s diagnosis is practically based on small amounts of tissue material. Secondly, tissue samples from NSCLC pa- tients can be difficult to obtain since the lesions frequently develop in inaccessible locations [22] . For these patients, a more acceptable type of sample would be liquid biopsy, as an alternative to tissue re-biopsy. Although liquid biopsy generally contains a low concentration of circulating tumor biomarkers, highly sensitive and precise technologies such as ddPCR technology can overcome this drawback [25] . With its great sensitivity, ddPCR can accurately iden- tify a mutant allele present at low frequency in a wild- type background. Since this technology has an advantage in mutation detection at low frequency, ddPCR has en- abled more significant implementation of liquid biopsy in molecular diagnostics with the aim of early diagnosis of tumors, minimally invasive monitoring of disease, and therapy response assessment [25] . In this way, the sampling of patients is significantly facilitated and enables regular monitoring of the patient’s healthcare condition. In 2019, Salihefendić et al. [5] studied whether ddPCR technology could be used as a confirmatory method for the detection and quantification of somatic mutations, previ- ously detected by NGS. A total of 35 samples from CRC and NSCLC patients were analyzed, and the results showed that there were no statistically significant differences between the results obtained by NGS and ddPCR methods. Therefore, high sensitivity and resolution of ddPCR, make it an adequate method for validating low-frequency somatic mutations [5] . In research published in 2016, Zheng et al. [27] report- ed that monitoring the status of cfDNA from plasma in NSCLC patients treated with TKI therapy can enable the detection of the acquired T790M mutation up to 6.8 months before the clinical progression of the patient’s condition. In their research, almost half of the detected T790M positive patients were detected from plasma samples before dis- ease progression (45.7%), and the time of detection varied from 0.8 to 6.8 months before clinical progression [27] . For patients with detected EGFR mutation who receive TKI therapy, regular analysis of the EGFR gene during treat- ment is significant in order to detect the T790M or other secondary mutations and to change the therapy.

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