Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

Abstract

Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next‐generation deep sequencing of TP53—a highly mutated and informative gene in GAC—to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash—GW). We evaluated their potential to reveal tumor‐derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon‐capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post‐treatment (196 samples), with high vertical coverage >8,000×. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW‐ (15.2%) and 6/46 PL‐samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW‐exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene‐panel designed for this malignancy.

RETRACTED: Exosomes Carrying MicroRNA-155 Target Forkhead Box O3 of Endothelial Cells and Promote Angiogenesis in Gastric Cancer

“…As one of the diseases that seriously endangers human health, GC has caused nearly 780,000 deaths worldwide in 2018, according to recent statistics 1 . The majority of GC patients are diagnosed at an advanced stage and, consequently, have already lost their best chances of treatment 28 . A vital reason for this phenomenon is that GC has a powerful capacity to generate new blood vessels, leading to continuous proliferation, metastasis, and rapid deterioration 29 .…”

Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

“…Besides blood, other biofluids, such as urine [7,23,28,37,39,47,52], cerebrospinal fluid (CSF) [60], and gastric washes [54], have been shown to harbor ctDNA. Depending on the type of cancer, tumors might more closely contact with different fluids that, consequently, might contain higher ctDNA concentrations than blood [23].…”

Recent advances in gastric cancer early diagnosis

“…The results showed that tp53 mutations were identified in 15/46 biopsies (32.6%), 7/46 gastric wash - (15.2%) and 6/46 plasma samples (13%). The authors suggested that gastric wash could be useful to detect DNA alterations using a comprehensive gene-panel designed for GC diagnosis[47].…”