Identification of Potential Genomic Alterations Using Pan-Cancer Cell-Free DNA Next-Generation Sequencing in Patients With Gastric Cancer

Abstract

Background: Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC.Methods: Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer Cell-Free Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively.Results: Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most.Conclusions: Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma

“…Specific to FGF signaling, particularly FGF1-FGFR2, showed significant activation only in tumor samples. Furthermore, FGFR2 overexpression is linked to a poor diagnosis and treatment response [ 33 ], and its rearrangement or fusion is concentrated in intrahepatic cholangiocarcinoma [ 34 , 35 ]. Previous studies have shown that key downstream signaling pathways altered by FGF-FGFR activation are the PI3K-AKT-mTOR pathway [ 36 ], which plays a central role in multiple oncogenic signaling pathways that drive tumorigenesis and progression [ 37 ].…”

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

“…One of the key advantages of NGS in colorectal cancer is its ability to simultaneously examine multiple genes and genetic mutations within a single test. This high-throughput capability allows for the identification of clinically relevant genetic alterations, such as mutations in KRAS, NRAS, BRAF, and other genes, which are critical for determining treatment options. , The identification of specific mutations or gene expression patterns in the tumor helps clinicians select the most appropriate targeted therapies or immunotherapies, enhancing treatment efficacy, and minimizing potential side effects. NGS also plays a pivotal role in uncovering rare or less common genetic alterations in colorectal cancer.…”

Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers

“…In an ongoing study, the identification of novel genomic alterations in cfDNA could hold actionable therapeutic interest, such as ERBB2, FGFR2, and TP53 in 4.9%, 6.2%, and 38.3%, respectively. The identification of these mutations could distinguish GC cases from others ( Kim et al, 2024 ). In PDAC patients, the Microsatellite Instability (MSI)-high status is usually assessed for therapy using immune checkpoint inhibitor drugs like pembrolizumab, nivolumab, or those administered with ipilimumab.…”