Published online Oct 14, 2018. doi: 10.3748/wjg.v24.i38.4412
Peer-review started: May 21, 2018
First decision: June 21, 2018
Revised: August 2, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 14, 2018
Processing time: 145 Days and 20 Hours
Gastric polyposis is a rare disease. Not all polyps progress to cancer. Monoallelic mutation in Fanconi anemia (FA) genes, unlike biallelic gene mutations that causes typical FA phenotype, can increase risks of cancers in a sporadic manner. Aberrations in the FA pathway were reported in all molecular subtypes of gastric cancer. We studied a patient with synchronous gastric cancer from gastric polyposis by conducting a 13-year long-term follow up. Via pathway-driven massive parallel genomic sequencing, a germline mutation at FANCA D1359Y was identified. We identified several recurrent mutations in DNA methylation (TET1, V873I), the β-catenin pathway (CTNNB1, S45F) and RHO signaling pathway (PLEKHG5, R203C) by comparing the genetic events between benign and malignant gastric polyps. Furthermore, we revealed gastric polyposis susceptible genes and genetic events promoting malignant transformation using pathway-driven targeted gene sequencing.
Core tip: The genetic events that predispose benign polyps to carcinoma are rarely explored in gastric cancer. We studied a rare case that progressed from benign gastric polyposis to gastric cancer and disclosed a monoallelic germline mutation (D1359Y) at Fanconi’s anemia gene, which may contribute to the phenotype. Comparing the genetic events between benign and malignant gastric polyps, several recurrent mutations in DNA methylation (TET1, V873I), the β-catenin pathway (CTNNB1, S45F) and RHO signaling pathway (PLEKHG5, R203C) were identified.