Case Report
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2018; 24(38): 4412-4418
Published online Oct 14, 2018. doi: 10.3748/wjg.v24.i38.4412
FANCA D1359Y mutation in a patient with gastric polyposis and cancer susceptibility: A case report and review of literature
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
Jeffrey Peng Huang, Johnson Lin, Kuei-Fang Chou, Ying-Wen Su, Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 10491, Taiwan
Chi-Yuan Tzen, Department of Pathology, Mackay Memorial Hospital, Taipei 10491, Taiwan
Wen-Yu Huang, Laboratory of Good Clinical Research Center, Mackay Memorial Hospital, Tamsui Branch, New Taipei City 25160, Taiwan
Chia-Chi Tsai, Department of General Surgery, Mackay Memorial Hospital, Taipei 10491, Taiwan
Chih-Jen Chen, Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 10491, Taiwan
Yen-Jung Lu, ACT Genomics Co., Ltd., Taipei 11494, Taiwan
Author contributions: Su YW contributed to the conception and design of the work; Huang JP, Tzen CY, and Su YW collected the patient’s clinical data and drafted the manuscript; Huang WY performed the research; Lu YJ and Su YW analyzed the data; Lin J, Tsai CC, Chen CJ and Chou KF helped to draft the manuscript; all authors read and approved the final manuscript.
Supported by the Mackay Memorial Hospital, No. MMH-106-62.
Informed consent statement: Informed consent was obtained from the patient.
Conflict-of-interest statement: All authors declare no conflict-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ying-Wen Su, MD, PhD, Doctor, Staff Physician, Division of Hematology and Medical Oncology, Department of Internal Medicine, Mackay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, Taipei 10491, Taiwan. yingwensu.5896@mmh.org.tw
Telephone: +886-2-25433535 Fax: +886-2-28098746
Received: May 21, 2018
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
Abstract

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.

Keywords: Gastric polyposis; Gastric cancer; Adenocarcinoma; Fanconi’s anemia; Malignant transformation

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.