Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome  

作　　者：Zhi Zhang Fu-Xiao Duan Guo-Li Gu Peng-Fei Yu 

机构地区：[1]Air Force Clinical College(Air Force Medical Center)of Anhui Medical University,Beijing 100142,China [2]Department of General Surgery,the General Hospital of Northern Theater Command PLA,Shenyang 110016,Liaoning Province,China [3]Department of General Surgery,Air Force Medical Center,PLA,Beijing 100142,China

出　　处：《World Journal of Gastroenterology》2020年第16期1926-1937,共12页世界胃肠病学杂志（英文版）

基　　金：Supported by Major Projects of the Chinese PLA"Thirteenth Five-Year Plan"Logistics Research Subject,No.AKJ15J003;No.AKJ15J001;Incubation Project of Military Medical Science and Technology Youth Cultivation Program,No.17QNP023;Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122.

摘　　要：BACKGROUND 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.AIM 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.METHODS 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.RESULTS 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.CONCLUSION 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.

关 键 词：PEUTZ-JEGHERS syndrome STK11 GENE LKB1 GENE Sequencing Genetic analysis 

分 类 号：R735[医药卫生—肿瘤]