FANCA D1359Y mutation in a patient with gastric polyposis and cancer susceptibility: A case report and review of literature  

作　　者：Jeffrey Peng Huang Johnson Lin Chi-Yuan Tzen Wen-Yu Huang Chia-Chi Tsai Chih-Jen Chen Yen-Jung Lu Kuei-Fang Chou Ying-Wen Su 

机构地区：[1]Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital [2]Department of Pathology, Mackay Memorial Hospital [3]Laboratory of Good Clinical Research Center, Mackay Memorial Hospital, Tamsui Branch [4]Department of General Surgery, Mackay Memorial Hospital [5]Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital [6]ACT Genomics Co., Ltd.

出　　处：《World Journal of Gastroenterology》2018年第38期4412-4418,共7页世界胃肠病学杂志（英文版）

基　　金：Supported by the Mackay Memorial Hospital,No.MMH-106-62

摘　　要：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.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.

关 键 词：GASTRIC POLYPOSIS GASTRIC cancer ADENOCARCINOMA Fanconi’s ANEMIA MALIGNANT transformation 

分 类 号：R57[医药卫生—消化系统]