Detection of ALK, RET, ROS1, and NTRK1 Rearrangements in Liquid and Volatile Biopsy Samples in the Treatment of Lung Cancer using Next-Generation RNA Sequencing

Project no. 20500 · Status: Kapanmış · 2021

Summary

Lung cancer (LC) is the most common malignancy worldwide and remains the leading cause of cancer-related death. Numerous genes play a pivotal role in the molecular pathology of LC. The identification of therapeutically targetable mutations and gene fusions in LC has not only transformed the clinical management of the disease but also revolutionized the procedures and techniques employed for its diagnosis and treatment. As approximately two-thirds of cases are diagnosed at advanced stages, the molecular changes occurring in tumors lead to resistance against multiple treatment modalities. The emergence of therapies that target fusion proteins resulting from gene fusions emphasizes the importance of routinely detecting these rearrangements in patients with lung adenocarcinoma. Tumor tissue biopsies are critical for detecting and analyzing the molecular changes necessary for accurate diagnosis and treatment decisions throughout the disease course. However, obtaining such biopsies is not always easy as they require invasive methods and fail to provide real-time monitoring of the molecular structure of the disease and its changes. New non-invasive analytical methods are needed to enable repeated and continuous monitoring of these molecular analyses. Until recently, mutations in LC were detected through labor-intensive methods such as RT-PCR and Sanger sequencing, while gene fusions were traditionally identified using FISH, IHC, or RT-PCR. However, the introduction of next-generation sequencing (NGS) methods has revolutionized this process. NGS enables the simultaneous sequencing of large numbers of short DNA and RNA sequences, providing a cost-effective approach to detect multiple genetic changes in numerous samples simultaneously. The main objective of this project is to develop easily reproducible new non-invasive methods, such as liquid biopsy (blood) and volatile biopsy (exhaled breath condensate), to detect fusion transcripts formed in ALK, RET, ROS1, and NTRK1 genes. These fusion transcripts are known to be effective in the development of drug resistance in the treatment of LC. The detection of these fusion transcripts will be done using the next-generation RNA sequencing (SeqRNA) method with the Ion AmpliSeq RNA Fusion Lung Cancer Research Panel.

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