title: Genetic Screening and Analysis of LKB1 Gene in Chinese Patients with Peutz-Jeghers Syndrome.
abstract: BACKGROUND Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disease. It severely decreases patient quality of life and leads elevated cancer risk. Germline mutation of LKB1 is the leading cause of familial PJS. MATERIAL AND METHODS To characterize the germline mutation of LKB1 gene in Chinese familial and sporadic PJS patients, 14 PJS families, 5 sporadic PJS patients, and 250 healthy adults were collected and genomic DNAs of peripheral blood were extracted. Mutation screenings of LKB1 were performed using MLPA (multiplex ligation-dependent probe amplification), PCR, direct sequencing, and PCR-DHPLC (denaturing high-performance liquid chromatography). RESULTS A total of 12 kinds of germline mutations were found in 9 familial PJS patients, most of which were point mutations (7/12); 4 large deletions of LKB1 were also observed. Of the 12 mutations, 7 were pathogenic (2 were de novo), 4 were just polymorphisms, and 1 was indefinitely pathogenic. No pathogenic mutation in exons of the LKB1 gene was detected in the 5 sporadic PJS patients. The mutation detection rate for the LKB1 gene was 85.7% in our Chinese familial PJS and 63.2% in all Chinese PJS patients. Eight familial PJS patients were identified with pathogenic germline mutations in 14 unrelated families (57.1%). Further methylation detection and analysis showed promoter methylation in carcinomatous polyps. CONCLUSIONS LKB1 gene germline mutation with pathogenic effect is a common cause of familial PJS in Chinese patients; however, it is not the only molecular pathogen of PJS. Methylation in the LKB1 gene promoter region may cause carcinomatous change in intestinal polyps.
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Laboratory of Genetics and Molecular Biology, Jiangsu Province Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China (mainland).
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Nanjing, Jiangsu, China (mainland).
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Fangyu
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Zhenkai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Heng
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Juan
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Haijun
authors.initials: H
authors.lastname: Wan
authors.affiliation: Laboratory of Genetics and Molecular Biology, Jiangsu Province Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China (mainland).
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Laboratory of Genetics and Molecular Biology, Jiangsu Province Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China (mainland).
authors.forename: Senqing
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Medicine, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland).
authors.forename: Jiong
authors.initials: J
authors.lastname: Liu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D005091:Exons; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008745:Methylation; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011788:Quality of Life; D017384:Sequence Deletion
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases