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 autosomal dominant genetic disease, which belongs to the category of hereditary colorectal cancer. It is currently believed that the occurrence of PJS is closely related to mutations in the LKB1/STK11 gene, and that different types of mutations have different effects on clinical phenotype. The genetic heterogeneity of PJS is obvious, and no other pathogenic genes have been found except the STK11 gene, and the relationship between genotype and phenotype is not clear.
This study aimed to investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS and discuss its relationship with the clinicopathological data of PJS.
To investigate mutations in genetically-related genes, try to explain the genetic heterogeneity of the disease, and investigate whether the disease has a relatively clear genotype-phenotype relationship.
Twenty patients with PJS were randomly selected for this study who were treated in the Air Force Medical Center and their clinicopathological data were collected, including family history, polyp distribution, polyp load, and internal or surgical intervention. Next-generation sequencing technology was used to study the mutation status of the genetically-related genes in PJS hamartoma polyp tissues, and examine the relationship between the mutation status of these genes and the clinical pathological data of PJS.
LKB1/STK11 gene mutations were detected in 16 of 20 cases, with 14 types of mutations, among which 8 new mutations were detected. 18 types of other gene mutations were detected in 9 of these 20 cases, all of which were heterozygous mutations. There was no statistical difference between mutations and family history, and between mutations and blackspot age. The maximum diameter of colorectal polyps was greater in the presence of LKB1/STK11 mutations.
We found a series of gene mutation types in hamartoma polyp tissues of PJS patients, and destruction of the MMR system may play an important role in the development course of some PJS patients. The colorectal hamartoma polyps with LKB1/STK11 mutations were larger than those with other gene mutations.
Improvements in gene sequencing technology and the identification of new mutation sites of STK11 and other possible pathogenic genes are necessary to describe the pathogenesis of PJS at the genetic level. In addition, an investigation into whether the disease has a relatively clear genotype-phenotype relationship is a hot spot for future research.