# Detection of Oncogene Hotspot Mutations in Female NSCLC Tumor DNA and Cell-Free DNA

## TL;DR

The study compares tumor DNA and cell-free DNA in female NSCLC patients to detect oncogene mutations, finding tumor DNA more effective but suggesting potential for plasma-based diagnostics.

## Contribution

Demonstrates the potential of cell-free DNA in plasma for detecting early-stage lung cancer mutations, despite lower detection rates compared to tumor DNA.

## Key findings

- Target mutations were detected in 38 out of 51 tumor tissue samples but only in 10 plasma samples.
- Early-stage lung cancer patients had detectable mutations in plasma, including EGFR deletions and TP53/MET SNPs.
- Later-stage cancers contributed more cfDNA to plasma, making extraction easier.

## Abstract

Non-small-cell lung cancer is the most prevalent type of lung cancer, with extensively characterized mutational spectra. Several biomarkers (such as EGFR, BRAF, KRAS gene mutations, etc.) have emerged as predictive and prognostic markers for lung cancer. Unfortunately, the quality of the available tumor biopsy and/or cytology material is not always adequate to perform the necessary molecular testing, prompting the search for alternatives. Cell-free DNA found in plasma is emerging as a highly promising avenue or a supplementary method for assessing the efficacy of cancer treatments. In this study, 51 Lithuanian females with non-small-cell lung cancer were studied. From each woman, two samples were obtained: lung tumor and plasma. Target mutations were identified in 38 out of 51 patients in tumor tissue samples, while in plasma samples, they were identified in only 10 patients’ samples. Theoretically, cfDNA from plasma could be a superior tool for lung cancer diagnostics and the detection of early cancer stages. Therefore, further improvements in cfDNA extraction and detection methods from plasma are needed, including the development of superior detection kits and analysis tools.

Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, with extensively characterized mutational spectra. Several biomarkers (such as EGFR, BRAF, KRAS gene mutations, etc.) have emerged as predictive and prognostic markers for NSCLC. Unfortunately, the quality of the available tumor biopsy and/or cytology material is not always adequate to perform the necessary molecular testing, prompting the search for alternatives. Cell-free DNA (cfDNA) found in plasma is emerging as a highly promising avenue or a supplementary method for assessing the efficacy of cancer treatments. This is especially valuable in instances where conventional biopsy specimens, like formalin-fixed, paraffin-embedded (FFPE), or freshly frozen tumor tissues prove inadequate for conducting molecular pathology analyses subsequent to the initial diagnostic procedures. By leveraging cfDNA from plasma, clinicians gain an additional tool to gauge the effectiveness of cancer therapies, thereby enhancing their ability to optimize tailored treatment strategies. In this study, 51 Lithuanian females with NSCLC were analyzed, with adenocarcinoma being the predominant pathology diagnosis in 40 cases (78%). Target mutations were identified in 38 out of 51 patients (74.5%) in tumor tissue samples, while in plasma samples, they were identified in only 10 patients’ samples (19.6%). Even though we did not have enough voluminous plasma samples in our study, gene mutations were detected in plasma from ten women, three of whom were diagnosed with early stages of lung cancer (stages I and II). For these patients, the following mutations were detected: deletion in exon 19 of the EGFR gene and single nucleotide polymorphisms in the TP53 and MET genes. All other women were diagnosed with stages III or IV of lung cancer. This indicates that the later stages of cancer contribute more cfDNA in plasma, making extraction less complicated.