Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome
Zhi Zhang1, Fu-Xiao Duan2, Guo-Li Gu3
1Air Force Clinical College (Air Force Medical Center) of Anhui Medical University, Beijing 100142, China.
Insights
Peutz-Jeghers syndrome (PJS) involves complex genetic mutations in hamartoma polyps, particularly in the LKB1/STK11 gene. Other gene mutations, including DNA mismatch repair genes, were also identified, impacting polyp size.
Area of Science:
- Genetics
- Oncology
- Gastroenterology
Background:
- Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by gastrointestinal polyps, mucocutaneous pigmentation, and increased cancer susceptibility.
- The clinical presentation and genetic underpinnings of PJS exhibit significant heterogeneity, with genotype-phenotype correlations remaining incompletely understood.
Purpose of the Study:
- To investigate the mutation profiles of hereditary colorectal tumor-associated genes within hamartoma polyp tissues from PJS patients.
- To explore the relationship between identified gene mutations and the clinicopathological characteristics of PJS.
Main Methods:
- Next-generation sequencing was employed to analyze 14 specific hereditary cancer-related genes in hamartoma polyp tissues from 20 PJS patients.
- Correlations between gene sequencing results and patient clinicopathological data were statistically analyzed.
Main Results:
- Mutations in the LKB1/STK11 gene were detected in 80% of patients, with 8 novel mutations identified.
- Mutations in other genes, including DNA mismatch repair (MMR) genes like MSH2 and MSH6, were found in 45% of cases, with several new mutations reported.
- Colorectal hamartoma polyps associated with LKB1/STK11 mutations were significantly larger in diameter compared to those with other gene mutations.
Conclusions:
- The genetic landscape of PJS hamartoma polyps is characterized by complex and diverse mutations, extending beyond the LKB1/STK11 gene.
- The presence of mutations in other genes, notably DNA mismatch repair (MMR) genes, highlights the multifaceted genetic etiology of PJS.
- LKB1/STK11 gene mutations are associated with larger polyp size, suggesting a potential impact on disease progression and clinical management.
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.
