Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Liquid biopsy using circulating tumor DNA (ctDNA) offers a non-invasive method for assessing tumor genomic alterations.
• Significant discordance exists between genomic alterations in matched tumor tissue and ctDNA samples, and even between different testing platforms.
• Investigating the causes of these discrepancies is essential for reliable clinical application.

Discussion:

• Parallel next-generation sequencing (NGS) panel testing of tumor tissue and ctDNA in 56 non-small cell lung cancer (NSCLC) patients was performed.
• Somatic mutations were detected in 63.6% of early-stage and 60% of advanced-stage NSCLC patients.
• Concordance between formalin-fixed paraffin-embedded tissue and cfDNA was 54.6% in early-stage and 80% in advanced-stage NSCLC.

Key Insights:

• Fresh frozen tumor samples did not improve concordance rates.
• Processing blood samples more than 4 hours after blood draw significantly reduced somatic mutation detection in cfDNA.
• Pre-analytical, analytical, and biological factors influence the concordance between tumor tissue and ctDNA genotyping.

Outlook:

• Parallel NGS testing of both tumor tissue and ctDNA may be necessary for accurate cancer targeted therapy guidance.
• This approach could potentially aid in the early detection of cancer.
• Further research is needed to optimize ctDNA analysis and improve concordance rates.