Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2020; 26(16): 1926-1937
Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1926
Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome
Zhi Zhang, Fu-Xiao Duan, Guo-Li Gu, Peng-Fei Yu
Zhi Zhang, Air Force Clinical College (Air Force Medical Center) of Anhui Medical University, Beijing 100142, China
Fu-Xiao Duan, Department of General Surgery, the General Hospital of Northern Theater Command PLA, Shenyang 110016, Liaoning Province, China
Guo-Li Gu, Peng-Fei Yu, Department of General Surgery, Air Force Medical Center, PLA, Beijing 100142, China
Author contributions: Zhang Z and Duan FX contributed equally to this study. Gu GL designed the research; Zhang Z, Duan FX and Yu PF collected and analyzed the clinical data; Zhang Z, Duan FX and Gu GL wrote the manuscript; Gu GL revised the manuscript.
Supported by Major Projects of the Chinese PLA "Thirteenth Five-Year Plan" Logistics Research Subject, No. AKJ15J003 and No. AKJ15J001; Incubation Project of Military Medical Science and Technology Youth Cultivation Program, No. 17QNP023; and Beijing Capital Medical Development Research Fund, No. Shoufa2020-2-5122.
Institutional review board statement: The Air Force Medical Center Ethics Committee reviewed and approved the study.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Guo-Li Gu, MD, MSc, Associate Professor, Chief Doctor, Department of General Surgery, Air Force Medical Center, PLA, No. 30 Fucheng Road, Haidian District, Beijing 100142, China.
Received: January 18, 2020
Peer-review started: January 18, 2020
First decision: February 27, 2020
Revised: February 29, 2020
Accepted: April 4, 2020
Article in press: April 4, 2020
Published online: April 28, 2020

Peutz-Jeghers syndrome (PJS) is a rare disease with clinical manifestations of pigmented spots on the lips, mucous membranes and extremities, scattered gastrointestinal polyps, and susceptibility to tumors. The clinical heterogeneity of PJS is obvious, and the relationship between clinical phenotype and genotype is still unclear.


To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.


Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center (former Air Force General Hospital) PLA between 2008 and 2017. Their hamartoma polyp tissues were used for APC, AXIN2, BMPR1A, EPCAM, MLH1, MLH3, MSH2, MSH6, MUTYH, PMS1, PMS2, PTEN, SMAD4, and LKB1/STK11 gene sequencing using next-generation sequencing technology. The correlations between the sequencing results and clinical pathological data of PJS were analyzed.


Fourteen types of LKB1/STK11 mutations were detected in 16 cases (80.0%), of which 8 new mutations were found (3 types of frameshift deletion mutations: c.243delG, c.363_364delGA, and c.722delC; 2 types of frameshift insertions: c. 144_145insGCAAG, and c.454_455insC; 3 types of splice site mutations: c.464+1G>T, c.464+1G>A, and c.598-1G>A); 9 cases (45.0%) were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11. Of these, MSH2: c.792+1G>A, MSH6: c.3689C>G, c.4001+13C>CTTAC, PMS1: c.46C>t, and c.922G>A were new mutations.


The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse. Moreover, other gene mutations in PJS hamartoma polyp tissue were observed, with the exception of LKB1/STK11 gene, especially the DNA mismatch repair gene (MMR). Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.

Keywords: Peutz-Jeghers syndrome, STK11 gene, LKB1 gene, Sequencing, Genetic analysis

Core tip: Peutz-Jeghers syndrome (PJS) is currently considered an autosomal dominant inherited disease caused by germline mutations of the LKB1/STK11 gene. Gastrointestinal hamartoma polyps are one of the most common clinical manifestations. In order to investigate the mutation status of these familiar genetically-related genes in PJS hamartoma polyp tissues, high-throughput sequencing was used to analyze the mutations of related genes in PJS hamartoma polyps. In addition, the relationships between the mutation status and the clinical pathological data of PJS are discussed.