title: [Mutations of fragile histidine triad gene in Peutz-Jeghers syndrome and canceration].
abstract: OBJECTIVE
  Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease. Fragile histidine triad (FHIT) gene is an important tumor suppressor gene at the fragile sites region of 3p14. The authors' previous study suggested that PJS patients might have a susceptible gene at the region of 3p14.2. This study was designed to reveal the relationship between the variant of FHIT gene in PJS and its canceration.
  
  
  METHODS
  Mutations of FHIT gene in 15 PJS patients and 20 unaffected members in 6 PJS families were determined using denaturing high-performance liquid chromatography (DHPLC), polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and DNA sequencing techniques.
  
  
  RESULTS
  A non-sense mutation and a frame-shift mutation were identified at codon 54(GAA to TAA) (exon 6) which led to the change of the amino acid from glutamic acid (Glu) to stop codon, and a guanine insertion at codon 62 in exon 6 resulting in a premature stop codon TGA at codon 111 in one PJS patient. A homozygous deletion and a synonymous mutation were detected in exon 8. The homozygous deletion of exon 8 in FHIT gene was found in two polyps tissues and two cancerous tissues. And in 3 sporadic cases, the patients and their mothers have the same bands of SSCP and the same elution profiles of DHPLC when exon 8 was amplified. The DNA sequencing result showed that a synonymous mutation (polymorphism) occurred at codon 98 [CAT (H)-->CAC (H)], this mutation resulted in no change of amino acid. In addition, one base substitute from A to G mutation at 5'end, +42 nucleotide in intron 6 of FHIT gene was detected in seven patients and two unaffected members.
  
  
  CONCLUSIONS
  PJS patients have low frequency point mutation of FHIT gene and their cancerous tissues had homozygous deletions in FHIT gene. This study indicated that the mutations and deletions of FHIT gene in PJS may play a role in the development of PJS and their cancerations.
authors.affiliation: 264 Hospital of PLA, Taiyuan, Shanxi, 030001, P. R. China. zhaoxirong@yahoo.com
authors.forename: Xi-Rong
authors.initials: XR
authors.lastname: Zhao
authors.forename: Lian-Chun
authors.initials: LC
authors.lastname: Kang
authors.forename: Yong-Shuang
authors.initials: YS
authors.lastname: Zhou
authors.forename: Yi-Xing
authors.initials: YX
authors.lastname: Jia
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Su-Hai
authors.initials: SH
authors.lastname: Kang
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Cui
authors.forename: An-Le
authors.initials: AL
authors.lastname: Sun
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Lu
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003062:Codon; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D010580:Peutz-Jeghers Syndrome / Q000209:etiology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D003062:Codon; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase