Germline mutations of the tumor suppressor gene LKB1/STK11 are responsible for the Peutz-Jeghers syndrome.
This syndrome is an autosomal-dominant disorder characterized by mucocutaneous pigmentation, hamartomatous polyps, and an increased risk of associated malignancies.
Dr Hamid Mehenni and colleagues from Switzerland assessed the presence of pathogenic mutations in the LKB1/STK11 gene in 46 unrelated Peutz-Jeghers syndrome families.
The research team undertook genotype-phenotype correlation in regard of the development of cancer in 170 Peutz-Jeghers syndrome patients belonging to these families.
All LKB1/STK11 variants detected with single-strand conformational polymorphism were confirmed by direct sequencing.
|59% had pathogenic mutations in the LKB1/STK11 gene |
|Digestive Diseases & Sciences|
Those without LKB1/STK11 mutation were further submitted to Southern blot analysis for detection of deletions/rearrangements.
The researchers performed statistical analysis for genotype-phenotype correlation.
In 59% of unrelated Peutz-Jeghers syndrome cases, the team identified pathogenic mutations in the LKB1/STK11 gene, including 9 novel mutations.
The new mutations were 2 splice site deletion-insertions, 2 missenses, 1 nonsense, and 4 abnormal splice sites.
Genotype-phenotype analysis did not yield any differences between patients carrying mutations in LKB1/STK11 vs those without mutations, even with respect to primary biliary adenocarcinoma.
Dr Mehenni's team concludes, "This study presents the molecular characterization and cancer occurrence of a large cohort of Peutz-Jeghers syndrome patients."
"It increases the mutational spectrum of LKB1/STK11 allelic variants worldwide, and provides a new insight useful for clinical diagnosis and genetic counseling of Peutz-Jeghers syndrome families."