CAJ | 학술논문

背景:近年来研究表明视网膜母细胞瘤(retinoblastoma,RB)的发生和病变的进展除了与已知的Rb1基因有相关性外,可能还有其他抑癌基因的参与.目的:探讨其他可能参与RB发生发展的基因存在的位点,并试图寻找和确定具有监测及预后价值的杂合性缺失(LOH)检测指标.设计:以RB患者为研究对象的病例分析.单位:一所军医大学医院的基因诊断治疗中心.对象:本研究在第三军医大学西南医院基因诊断治疗中心完成,研究对象为1998-05/2001-10在本校三所附属医院门诊就诊的RB患者16例.纳入标准:符合RB诊断标准的年龄小于3岁的患儿;排除标准:有家族遗传史者.其中男10例,女6例;累及双眼者12例,累及单眼者4例.方法:在患者的RB肿瘤及外周血标本中运用荧光聚合酶链反应(PCR)分别扩增13号染色体上14个微卫星DNA标记,分析测定各位点LOH发生率;同时通过家系分析确定位点缺失的遗传学来源.主要观察指标:患者13号染色体上LOH发生频率.结果:16例RB患者中,12例在13号染色体上1个或1个以上位点发生LOH.其中3个位点D13S265、D13S263和D13S153(位于Rb1基因内)LOH发生机率最高.12个LOH阳性标本中有10个位点的缺失被确定发生在父系来源的染色体中.LOH阳性及阴性组RB的确诊时间分别为504和1 086 d,两组相比差异具有显著性意义(t=2.357,P＜0.05).结论:LOH阳性组的患者RB确诊时间早于LOH阴性组.除已确定的Rb1基因外,D13S263(13q14.1-14.2)和D13S265(13q31-32)两个位点的LOH现象也可能对RB患者的早期干预和功能监测具有一定提示作用.
배경:근년래연구표명시망막모세포류(retinoblastoma,RB)적발생화병변적진전제료여이지적Rb1기인유상관성외,가능환유기타억암기인적삼여.목적:탐토기타가능삼여RB발생발전적기인존재적위점,병시도심조화학정구유감측급예후개치적잡합성결실(LOH)검측지표.설계:이RB환자위연구대상적병례분석.단위:일소군의대학의원적기인진단치료중심.대상:본연구재제삼군의대학서남의원기인진단치료중심완성,연구대상위1998-05/2001-10재본교삼소부속의원문진취진적RB환자16례.납입표준:부합RB진단표준적년령소우3세적환인;배제표준:유가족유전사자.기중남10례,녀6례;루급쌍안자12례,루급단안자4례.방법:재환자적RB종류급외주혈표본중운용형광취합매련반응(PCR)분별확증13호염색체상14개미위성DNA표기,분석측정각위점LOH발생솔;동시통과가계분석학정위점결실적유전학래원.주요관찰지표:환자13호염색체상LOH발생빈솔.결과:16례RB환자중,12례재13호염색체상1개혹1개이상위점발생LOH.기중3개위점D13S265、D13S263화D13S153(위우Rb1기인내)LOH발생궤솔최고.12개LOH양성표본중유10개위점적결실피학정발생재부계래원적염색체중.LOH양성급음성조RB적학진시간분별위504화1 086 d,량조상비차이구유현저성의의(t=2.357,P＜0.05).결론:LOH양성조적환자RB학진시간조우LOH음성조.제이학정적Rb1기인외,D13S263(13q14.1-14.2)화D13S265(13q31-32)량개위점적LOH현상야가능대RB환자적조기간예화공능감측구유일정제시작용.
BACKGROUND: Recent researches have indicated that the generation and development of retinoblastoma(RB) might also be related with other anti-oncogenes except the known Rb1 gene.OBJECTIVE: To explore the loci of other genes which possibly participated in RB generation and development and try to find and confirm the indicators for the loss of heterozygosity(LOH) with merits in surveillance and prognosis.DESIGN: A case analysis by employing RB patients as subjects SETTING: A center of gene diagnosis and therapy of a military medical university-affiliated hospitalPARTICIPANTS: The study was conducted in the center of gene diagnosis and therapy of Xinan Hospital affiliated to Third Military Medical University of Chinese PLA. Sixteen RB cases including 10 males and 6 females were the patients of the outpatient department of three-affiliated hospitals of the Third Military Medical University of Chinese PLA from May 1998 to October 2001.Inclusion criteria: in accordance with RB diagnostic criteria and younger than 3 years old; Exclusion criteria: family heredity history. Two eyes were involved in 12 cases and one eye was involved in 4 cases.METHODS: Fourteen micro-satellite DNA labels on the 13th chromosome in tumor or peripheral blood samples were separately amplified by polymerase chain reaction(PCR) to analyze the incidence of LOH of each locus. Simultaneously, the genetic source of loci loss was confirmed by genealogical analysis.MAIN OUTCOME MEASURES: Frequency of LOH incidence on the 13th chromosome.RESULTS: In 16 RB patients,LOH occurred in one or more than one locus on the 13th chromosome of 12 cases. Thereinto, the probability of LOH occurrence on three loci including D13S265,D13S263 and D13S153(in Rb1gene) was the highest. Ten loci of LOH in 12 LOH positive samples were confirmed from agnate chromosomes. The RB confirmation of LOH-positive group or LOH-negative group needed 504 days or 1086 days,which was significantly different(t=2. 357,P<0.05).CONCLUSION: RB confirmation was earlier in LOH-positive patients than LOH-negative patients. Except the confirmed Rb1 gene, LOH on two loci including D13S263(13q14.1-14.2) and D13S265 (13q31-32) also might have certain suggestive effect on early intervention and functional surveillance of RB patients.