title: Birt-Hogg-Dubé (BHD) gene mutations in human gastric cancer with high frequency microsatellite instability.
abstract: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited genodermatosis characterized by benign hamartomatous skin lesions and an increased risk of pneumothorax and renal tumors. Many of the patients harbor insertion/deletion mutations in the hypermutable poly(C)(8) tract in exon 11 of the BHD gene. This mutational hot spot is also reported to be a target of mutation in microsatellite instability (MSI) sporadic colorectal tumors. To test if the BHD gene is a potential mutational target in gastric cancer, we screened for mutations in all of the coding exons of the BHD gene in 30 cases of MSI gastric cancer as well as 50 cases of microsatellite stable (MSS) gastric cancer. Mutations in the poly(C)(8) tract of BHD were detected in 3 of 19 MSI-high cases (15.8%), and none of 11 MSI-low cases. All BHD mutated cases also showed mutations of both BAX and TGFbetaRII. No mutations were detected in the other exons of the BHD gene. No BHD mutations were found in MSS gastric cancer cases. Taken together, these findings show that the BHD gene is a rare target in MSI-high gastric cancer, and BHD mutation tends to occur downstream in the mutational events of other major MSI-high target genes.
authors.affiliation: Department of Surgery, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Jiang
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohtsuji
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsurumaru
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011066:Poly C / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; C476078:FLCN protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D011066:Poly C; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II