Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1926
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.
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.