Rare compound mutation of EGFR L858R and E709A identified in both solid tumor and liquid biopsy of a lung adenocarcinoma patient

Abstract

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer. Among NSCLC, lung adenocarcinoma is majorly characterized by driver activating mutations in the EGFR (Epidermal growth factor receptor) gene, covering exons-18, 19, and 21. The most frequently observed mutations are the classical mutations Exon–19 E746_A750 deletion, and Exon - 21 L858R, EGFR exon-18 G719X than the rare variants of these genes. Besides classical mutations and other rare mutations, compound mutations are not very profound. Here, in this present case report, we identified the rare occurrence of EGFR E709A and L858R in tissue and liquid biopsy sample of the patient. The identified compound mutation had been validated in FFPE (formalin fixed paraffin embedded) tissue sample by Sanger sequencing. In addition, the concordance of the rare variants in tumor tissue as well as liquid biospy strongly suggests the clinical utility of liquid biopsy. The patient had been treated with single agent gefitinib which showed mixed response and later treatment had been upgraded to pemetrexed + carboplatin + gefitinib. The sensitivity and specificity of NGS technology provide an opportunity to identify uncommon variants, which opens up a wider avenue for targeted therapeutics.