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Abstract

TO WHAT EXTENT TUMOR CELL-FREE DNA (CFDNA) EXTRACTED FROM PERIPHERAL BLOOD CAN BE USED TO DETECT EGFR MUTATIONS AS AN ALTERNATIVE SOURCE TO THE TUMOR DNA EXTRACTED FROM PARAFFIN EMBEDDED TISSUE IN PATIENTS WITH LUNG ADENOCARCINOMA WHO ARE NOT FIT FOR INVA

Hussam S. Aziz*, Jasim M.A. Al-Diab and Saad A. Alomar

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Abstract

Epidermal growth factor receptor (EGFR) mutations occur in about 30- 40% of patients with adenocarcinoma. The presence of certain EGFR mutations, such as G719X, S768I, and L861Q may impact the selection of tyrosine kinase inhibitor (TKI) type for best response, whereas tumors harboring other mutations, e.g. T790M mutation renders the tumor resistant to most first and second generation TKI that requires treatment with third generation TKI, like osimertinib. Also the type of detected mutations may help in assessing the prognosis of the disease. Therefore, oncologists usually rely on detection of EGFR mutations in patients with lung adenocarcinoma prior to starting the therapy of the patient in order to select the best treatment regimen. The detection of EGFR mutations is usually done by testing DNA extracted from paraffin embedded tissue. However, some patients are not fit for invasive sampling from the tumor itself; therefore we conducted this study to assess the sensitivity of detecting EGFR mutations in circulating cell-free tumor DNA (cfDNA) extracted from the patients’ plasma. To reach our goal, we enrolled patients with lung adenocarcinoma who were already diagnosed to have EGFR mutations detected in DNA extracted from their FFPE tissue, and then we test for the presence of the corresponding mutations in ctDNA extracted from the patients’ peripheral blood. Objectives: Assessing the sensitivity of EGFR mutation detection in cfDNA extracted from peripheral blood in comparison with EGFR mutation detection in DNA extracted from paraffin embedded tissues and assessing the feasibility of using peripheral blood as an alternative to the invasive tumor biopsy sampling in detecting EGFR mutations in patients with lung adenocarcinoma.

Keywords: EGFR, lung adenocarcinoma, cfDNA, mutation detection.


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