Rare compound mutation of EGFR L858R and E709A identified in lung adenocarcinoma patient

Karkinos Healthcare, in collaboration with Tata Memorial Hospital, the Institute of Bioinformatics, and other institutions, reported the identification of a rare compound mutation of EGFR  L858R and E709A in both solid tumour and liquid biopsy of a lung adenocarcinoma patient, highlighting an advancement in the field of lung cancer research, diagnosis and treatment. 

Key findings:  

• Rare co-occurrence: This case report highlights the rare co-occurrence of EGFR E709A and  L858R in non-small cell lung cancer (NSCLC) from an Indian patient, identified in both tumour tissue and liquid biopsy samples.  
• Compound mutation impact: Canonical EGFR mutations, such as exon-19 deletion or L858R, may not respond similarly to tyrosine kinase inhibitors (TKIs) when harbouring a compound mutation with rare variants.  
• NGS methodology: The study underscores the importance of using Next-Generation  Sequencing (NGS) based methodology to evaluate a broader spectrum of variants, guiding better clinical management.  

Lung cancer is one of the most prevalent cancers in India, often diagnosed at a late stage.  NSCLC, the most common subtype, accounts for more than 80 per cent of all lung cancer cases. Among NSCLC,  EGFR mutations are significant biomarkers used by clinicians for treatment decisions. The Exon 19  deletion and L858R mutations constitute 90 per cent of EGFR mutations. However, compound mutations,  which involve more than one EGFR mutation within the same tumour, are a heterogeneous subgroup of rare mutations.  

The study led by Dr Prashant Kumar, Chief Scientific Officer, Karikinos Healthcare employed NGS technology to identify a unique case of the co-occurrence of EGFR E709A and  L858R in tissue and liquid biopsy samples from a 42-year-old female patient with NSCLC. This rare compound mutation was validated in FFPE (formalin-fixed paraffin-embedded) tissue samples using  Sanger sequencing. The patient initially showed a mixed response to single-agent gefitinib treatment,  prompting a subsequent treatment regimen upgrade to pemetrexed, carboplatin, and gefitinib.  

This discovery demonstrates the clinical utility of liquid biopsy in identifying rare mutations, aiding in more accurate diagnostics and personalised treatment plans. The sensitivity and specificity of NGS technology provide opportunities to identify uncommon variants, paving the way for targeted therapeutics and improved patient outcomes.