Genomic landscape of epithelium with low-grade atypia on gastric cancer after Helicobacter pylori eradiation therapy
JGastroenterol_54_907.pdf 5.73 MB
Nelson, Hayes Clair
Eradiation therapy for Helicobacter pylori
Epithelium with low-grade atypia
Background Gastric cancer may develop after successful eradication of Helicobacter pylori, although the incidence is lower than in non-eradicated individuals. We previously reported the appearance of characteristic epithelium with low-grade atypia (ELA) on the surface of gastric cancer after H. pylori eradication. However, whether ELA originates from cancer after re-differentiation or from the non-cancerous surrounding mucosa is unknown.
Methods We isolated ELA regions from 10 early gastric cancer patients and analyzed the nucleotide sequences for 90 oncogenes and 35 fusion oncogenes, comparing them with counterpart cancer tissue, normal gastric mucosa, and blood cell-derived DNA. Somatic mutations in each tissue were identified by comparing them with the sequences from whole blood-derived DNA.
Result Gene alterations were observed in nine of the ten patients, and up to 42 and 70 somatic mutations were seen in cancer and ELA samples, respectively. Common mutations shared between cancer and ELA tissues were found in eight of these nine patients. In contrast, common mutations between non-cancer mucosa and ELA were only detected in one patient, who also had common mutation between cancer and ELA. ELA-specific nucleotide substitutions were seen in seven patients. In contrast, cancer-specific substitutions were only found in two patients. 18 out of 19 amino acid substitutions present in cancer tissue were also identified in ELA. These results suggest that ELA originated from cancer tissue and accumulated further nucleotide substitutions.
Conclusions Differential diagnosis of ELA and normal mucosa should be carefully performed to prevent misdiagnosis of ELA as normal mucosa with atypia.
This study was supported by grants from the Japan Society for the Promotion of Science (JSPS KAKENHI GrantNumber: 16K19379; https://www.jsps.go.jp/j-grantsinaid/).
Journal of Gastroenterology
© The Author(s) 2019
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.