Genomic characterization in gastrointestinal cancer patients based on cfDNA sequencing

e15507 Background: Gastrointestinal cancer (GIC) is one of the most prevalent cancers worldwide. Late stages diagnosis is one of the main reasons for poor prognosis of GIC. The invasive nature of endoscopy assay has greatly decrease the willingness for early screening, nearly 50% of patients diagnosed with GIC were in advanced stages. With the advanced of next-generation sequencing (NGS) technology, liquid biopsy has quickly gaining interest in early cancer screening. In order to address the poor prognosis of GIC, mutation features and potential biomarkers were investigated using NGS data from 169 Chinese GIC patients with blood derived cell-free DNA (cfDNA). Methods: Blood-derived cfDNA sampels were collected from Chinese patients with colorectal cancer (CRC) (n = 121) and gastric cancer (GC) (n = 48) and then performed pan-cancer sequencing panel targeting 680 cancer-related genes. Genomic alterations of single nucleotide variations, short indels and tumor mutation burden were analyzed. Two-sided Fisher’s exact test was used for all statistical analyses. COSMIC data was retrieved from COSMIC database version 97. Results: Among GC patients, the proportion of patients possessing mutations in TP53 (43.75% vs 37%, p = 0.49) and KRAS (10.42% vs 5.6%, p = 0.19) showed consistent distribution with COSMIC database. While KIT (14.58% vs 3.42%, p = 0.0014) and SYNE1 (10.42% vs 30.8%, p = 0.0021) showed varied distribution outcomes. CRC patient cohort also showed coherent distribution compared with COSMIC database. No significant difference was detected between the two cohorts in TP53 (51.5% vs 44.57%, p = 0.085), KRAS (36.53% vs 32.33%, p = 0.24), APC (44.91% vs 47.74%, p = 0.48) and PIK3CA (14.37% vs 14.10%, p = 0.91). However, the proportion of SYNE1 mutation is still significantly lower than in the COSMIC database (17.37% vs 29.31%, p = 0.0006). As all patients from the study cohort are Chinese, whether a lowered occurrence of SYNE1 mutation is specific to Chinese or certain region can be further studied. Conclusions: This study revealed that the mutational landscape of liquid biopsy cfDNA sequencing is highly consistent with existing database, which has consolidated the feasibility of liquid biopsy in early cancer detection. Besides, this study also revealed a lowered occurrence of SYNE1 and increased KIT mutation in the cohort. While increased KIT mutation can be explained by the proportion of recruited gastrointestinal stromal tumor patients, the lowered SYNE1 can provide new insights into region-specific diagnosis and treatment selection.