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背景与目的:Peutz-Jeghers综合征(Peutz-Jegherssyndrome,PJS)是一种常染色体显性遗传性疾病。脆性组氨酸三连体(fragilehistidinetriad,FHIT)基因是定位于3p14.2脆性位点区域的重要抑癌基因。我们以往的研究结果认为PJS患者在3p14.2区域可能存在易感基因。本文旨在明确PJS患者FHIT基因突变与癌变的关系和FHIT基因的改变及规律。方法:应用变性高效液相色谱(DHPLC)分析、聚合酶链反应-单链构象多肽分析技术(PCR-SSCP)和DNA测序方法,对6个PJS家系中的15个患者及其20例正常家族成员的FHIT基因进行了研究。结果:在6个家系中,有1位患者的FHIT基因第159位核苷酸由G→T,相应的第54位密码子编码的氨基酸由谷氨酸变成终止密码子;在第62位密码子处存在碱基G插入,使读码框架发生移位,在第111位密码子处提前出现终止密码子;在2例癌变患者的息肉标本DNA和癌标本DNA中检测到FHIT基因第8外显子的纯合性缺失;在3个散发的PJS患者中发现,患者与其母亲在第8外显子,有相同的SSCP带型和DHPLC峰型,DNA测序结果显示,在第98位密码子处发生同义突变,由CAT→CAC,相应编码的氨基酸未发生改变,均为苏氨酸。另外,有7例患者和2例正常人在FHIT基因的第6内含子5’端第42位核苷酸位点发生由A→G的点突变。结论:FHIT基因在PJS患者中存在点突
Background and Objective: Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease. Fragile histidine triad (FHIT) gene is an important tumor suppressor gene located in the 3p14.2 fragile locus. Our previous findings suggest that PJS patients may have susceptibility genes in the 3p14.2 region. This article aims to clear PJS patients with FHIT gene mutation and cancer and FHIT gene changes and patterns. Methods: Fifteen of six PJS pedigrees and 20 normal controls were studied by denaturing high performance liquid chromatography (DHPLC), polymerase chain reaction-single chain conformational peptide analysis (PCR-SSCP) and DNA sequencing. Members of the FHIT gene were studied. RESULTS: Of the 6 pedigrees, 1 patient had the 159th nucleotide of FHIT gene changed from G → T and the corresponding amino acid encoded by codon 54 changed from glutamic acid to a stop codon. At position 62 There was a base G insertion at the codon, which shifted the reading frame and showed a stop codon at codon 111 in advance. FHIT gene 8 Homozygous deletion of exons; found in three sporadic PJS patients, patients with their mothers in exon 8, the same SSCP banding and DHPLC peak DNA sequencing results showed that in the 98th password Synonymous mutations occur at the sub-place, from CAT → CAC, the corresponding encoded amino acids did not change, are threonine. In addition, seven patients and two normal individuals developed a point mutation from A → G at the 42nd nucleotide position of the 5 ’end of the sixth intron of the FHIT gene. Conclusion: FHIT gene is spotted in PJS patients