The potential of cfDNA in gastroesophageal cancer: a comparative analysis of tissue and liquid biopsy by using NGS

Cancer is fundamentally a genetic disease; therefore, molecular characterization is essential for accurate diagnosis and treatment choice. Due to the genetic complexity of cancer, advanced technologies such as next-generation sequencing (NGS) are crucial. NGS has been implemented to detect rare and cancer-specific somatic mutations, becoming a powerful tool in cancer genetics. Deep sequencing and hybrid-capture-based enrichment, for instance, enables the detection of alterations in minimal DNA quantities, including circulating free DNA (cfDNA). The tumor-derived fraction of cfDNA holds potential as a diagnostic and prognostic biomarker and for therapy monitoring. Gastroesophageal cancers, a common cancer globally, shed good levels of cfDNA at advanced stages, while only small amounts at the first stages, limiting its clinical application. Despite this, these cancers exhibit alterations like single-nucleotide variants (SNVs) and copy-number variants (CNVs), which can be observed even in cfDNA. Comparing sequencing data from tissue biopsies with time-matched liquid biopsies reveals partial correspondence due to tumor heterogeneity, which tissue biopsies struggle to capture. Moreover, longitudinal liquid biopsy samples offer insights into tumor evolution, providing a minimally invasive approach for monitoring patients over time. This highlights the potential of cfDNA as a complementary tool in precision oncology, despite challenges in its current clinical utility.