摘要
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。
BACKGROUND &OBJECTIVE:Peutz-Jeg hers syndrome (PJS)is an autosomal dominantly inherite d disease.Frag ile histidine triad(FHIT)g ene is an important tumor suppressor g en e at the frag ile sites reg ion of 3p14.The authors'previous study sug g ested that PJS pa tients mig ht have a susceptible g ene at the reg ion of 3p14.2.This stu dy was desig ned to reveal the relatio nship between the variant of FHIT g ene in PJ S and its canceration.METHOD:Mutations of FHIT g ene in 15PJS patie nts and 20unaffected members in 6PJS families were determined using dena turing hig h-performance liquid chromatog raphy(DHPLC),polymerase chain reaction-sing le strand conformation polymorphism(PCR-SSCP)and DNA sequencing techniques.RESULTS :A non-sense mutation and a frame-shi ft mutation were identified at codon 54(GAA to TAA)(exon 6)which led to the chang e of the amino acid from g lutamic acid(Glu)to stop codon,and a g uanine insertio n at codon 62in exon6resulting in a premature stop codon TGA at codon 111in one PJS patient.A homozyg ous deletion and a synonymous mutation were detected in exon 8.Th e homozyg ous deletion of exon 8in FHIT g ene was found in two polyps tissues a nd two cancerous tissues.And in 3spora dic cases,the patients and their mot hers have the same bands of SSCP and the sam e elution profiles of DHPLC when exon8was amplified.The DNA sequencing r esult showed that a synonymous mutat ion(polymorphism)occurred at codon 98[CAT(H)→CAC(H)],this mutation resulted in no chang e of amino acid.I n addition,one base substitute from A to G mutation at 5'end,+42nucleotide in intron 6of FHIT g ene was detected in seven patients and two unaffected me mbers.CONCLUSION:PJS patients have low frequency point mutation of FHIT g ene and their cancerous tissues had homozyg ous deletions in FHIT g ene.T his study indicated that the mutatio ns and deletions of FHIT g ene in PJS may play a role in the development of PJS and th eir cancerations.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2003年第1期50-54,共5页
Chinese Journal of Cancer
基金
国家自然科学基金资助(批准号:39970816)
