Gu GL, Zhang Z, Zhang YH, Yu PF, Dong ZW, Yang HR, Yuan Y. Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome. World J Gastroenterol 2021; 27(39): 6631-6646 [PMID: 34754157 DOI: 10.3748/wjg.v27.i39.6631]
Corresponding Author of This Article
Ying Yuan, MD, PhD, Chief Doctor, Professor, Department of Medical Oncology, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. yuanying1999@zju.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Guo-Li Gu, Zhi Zhang, Yu-Hui Zhang, Peng-Fei Yu, Zhi-Wei Dong, Hai-Rui Yang, Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
Yu-Hui Zhang, Graduate School, Hebei North University, Zhangjiakou 075000, Hebei Province, China
Ying Yuan, Department of Medical Oncology, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Author contributions: Gu GL and Zhang Z contributed equally to this study; Gu GL and Yuan Y designed the research; Gu GL, Zhang Z, Yang HR, Yu PF, Dong ZW and Zhang YH conducted experiments and analyzed the clinical data; Gu GL and Zhang Z wrote the manuscript; and Yuan Y revised the manuscript.
Supported byBeijing Capital Medical Development Research Fund, No. Shoufa2020-2-5122.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Air Force Medical Center (Approval No. 2020-105-PJ01), and the Second Affiliated Hospital of Zhejiang University School of Medicine (Approval No. 2017-066).
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: All patients (legal guardians of minors) understood the process and purpose of this study and signed an informed consent form. In the process of sample collection, follow the principles of informed consent in the Declaration of Helsinki, the Universal Declaration of Human Genome and Human Rights, and the Declaration of the Human Genome Ethics Committee on DNA Sampling, Control, and Acquisition. 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ying Yuan, MD, PhD, Chief Doctor, Professor, Department of Medical Oncology, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. yuanying1999@zju.edu.cn
Received: April 15, 2021 Peer-review started: April 15, 2021 First decision: May 24, 2021 Revised: May 31, 2021 Accepted: August 11, 2021 Article in press: August 11, 2021 Published online: October 21, 2021 Processing time: 187 Days and 22.3 Hours
ARTICLE HIGHLIGHTS
Research background
Different types of pathogenic mutations may produce different clinical phenotypes, but no exact correlation between Peutz-Jeghers syndrome (PJS) genotype and clinical phenotype has been found so far. So it is necessary to study the correlation between genotype and clinical phenotype of PJS, and explore the internal molecular mechanism of different clinical phenotypes.
Research motivation
The authors included 24 cases of treated PJS cases as study participants, collected peripheral venous blood or normal tissue adjacent to polyps for high-throughput next-generation sequencing (NGS) of 139 hereditary colorectal tumor-related genes including STK11/LKB1 to study the correlation between genotype and clinical phenotype of PJS.
Research objectives
To investigate the correlation between the genotype and clinical phenotype of PJS.
Research methods
Twenty-four patients with PJS were randomly selected for study inclusion. A total of 139 common hereditary tumor-related genes including STK11/LKB1 were screened and analyzed for pathogenic germline mutations by high-throughput next-generation sequencing (NGS), and the pathogenicity of these mutations was evaluated.
Research results
STK11/LKB1 gene mutations were identified in 20 PJS patients, 90% of which were pathogenic mutations. 10 cases had new mutation sites. Pathogenic mutations were significantly less frequent in exon 7 of the STK11/LKB1 gene than in other exons. Truncation mutations were more common in exons 1 and 4, and their pathogenicity was significantly higher than that of missense mutations. We also identified SLX4 gene mutations in PJS patients.
Research conclusions
PJS has a relatively complicated genetic background. Changes in the sites responsible for coding functional proteins in exon 1 and exon 4 of STK11/LKB1 may be one of the main causes of PJS. Mutation of the SLX4 gene may help to explain the genetic heterogeneity of PJS.
Research perspectives
Exploration of the relationships of clinical phenotypes with different STK11 genotypes, may help to interpret some controversial research results. The detection of SLX4 gene mutations in patients with PJS was reported for the first time.
