Journal
DIGESTIVE DISEASES AND SCIENCES
Volume 59, Issue 8, Pages 1856-1861Publisher
SPRINGER
DOI: 10.1007/s10620-014-3077-7
Keywords
STK11; Peutz-Jeghers syndrome; P53; Mutation
Categories
Funding
- National Natural Science Foundation of China [81171678, 81100068]
Ask authors/readers for more resources
The serine/threonine kinase 11 (STK11) gene is the main causal gene in Peutz-Jeghers syndrome (PJS). Abnormal STK11 may increase cancer risk of PJS patients via affecting its target proteins such as P53, AMPK, and PTEN. In this study, we investigated the molecular basis of six Chinese PJS patients. Blood samples were collected from four Chinese PJS families and two sporadic patients. The entire coding region of the STK11 gene was amplified by polymerase chain reaction and analyzed by direct sequencing. Functions of mutants were assessed by PolyPhen-2, Swiss-Model software, and luciferase reporter assay. Novel mutations (c.842_843insC, c.804_805insG, and c.922T > G) and recurrent mutations (c.526G > A, c.180C > G, and c.1062C > G) were identified. Missense mutation c.922T > G and c.526G > A were predicted as probably damaging by PolyPhen-2, while c.1062C > G was benign. Mutation c.108C > G was a nonsense mutation. The 284Ter mutants of c.842_843insC and c.804_805insG significantly diminished the capacity of P53 activity in 293FT cells. Our results support that STK11 gene mutations underlie Chinese patients with PJS. Mutation involving partial kinase domain disrupts normal function of STK11. Our results also enlarge the spectrum of STK11 variants in PJS patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available