CAJ | 학술논문

在有丝分裂过程中BUBR1监视微管与着丝点的结合,是保证染色体均等分离的重要分子机制之一.BUBIB变异家谱研究及其敲除模型的研究表明,BUBR1缺陷与染色体不稳定性及肿瘤的发生直接相关.近来在数种人类肿瘤,对BUBR1蛋白过度表达有所报道.但在直结肠癌,BUBR1的过度表达是否与染色体不稳定性的发生有关目前仍无定论.在人类结直肠癌的遗传不稳定性主要表现为两种类型,染色体不稳定性及微卫星不稳定性,它们提示了两条独立的肿瘤发生路径.一般认为不存在高频度微卫星不稳定性表型的肿瘤通过染色体不稳定途径癌变.P53蛋白通过多种机制对维护遗传稳定性起到重要的作用,TP53基因突变经常与染色体不稳定现象并存.DNA倍体情况也是染色体不稳定研究不可缺少的指标.本研究采用免疫组织化学法检测了一组93例进展期散发结直肠癌BUBR1蛋白的表达情况,直接测序法检测TP53变异.高分辨率荧光标记微卫星不稳定检测技术检测微卫星状态,固相激光扫描细胞仪技术检测DNA倍体情况.我们分析了BUBR1表达与三种反映遗传背景的因子的关系.BUBR1蛋白过度表达在人结直肠癌较为常见.在非高频度微卫星不稳定的结直肠癌,BUBR1蛋白过度表达率明显为高(P＜0.01),在TP53基因突变的病例其过度表达率亦较高(P＜0.05).BUBR1蛋白的过度表达与DNA异倍体无统计学相关,但DNA异倍体病例的BuBRl过度表达有偏高倾向.BuBRl表达情况与常用的临床病理学指标无统计学相关.BuBRl过度表达同微卫星状态及TP53突变的关系明确的提示,在人类散发结直肠癌,BUBR1蛋白过度表达与染色体不稳定状态有关.BUBR1过度表达作为一种常见的分子异常,对于肿瘤的早诊预防提供新的标志物.并可能成为治疗的新靶点.
재유사분렬과정중BUBR1감시미관여착사점적결합,시보증염색체균등분리적중요분자궤제지일.BUBIB변이가보연구급기고제모형적연구표명,BUBR1결함여염색체불은정성급종류적발생직접상관.근래재수충인류종류,대BUBR1단백과도표체유소보도.단재직결장암,BUBR1적과도표체시부여염색체불은정성적발생유관목전잉무정론.재인류결직장암적유전불은정성주요표현위량충류형,염색체불은정성급미위성불은정성,타문제시료량조독립적종류발생로경.일반인위불존재고빈도미위성불은정성표형적종류통과염색체불은정도경암변.P53단백통과다충궤제대유호유전은정성기도중요적작용,TP53기인돌변경상여염색체불은정현상병존.DNA배체정황야시염색체불은정연구불가결소적지표.본연구채용면역조직화학법검측료일조93례진전기산발결직장암BUBR1단백적표체정황,직접측서법검측TP53변이.고분변솔형광표기미위성불은정검측기술검측미위성상태,고상격광소묘세포의기술검측DNA배체정황.아문분석료BUBR1표체여삼충반영유전배경적인자적관계.BUBR1단백과도표체재인결직장암교위상견.재비고빈도미위성불은정적결직장암,BUBR1단백과도표체솔명현위고(P＜0.01),재TP53기인돌변적병례기과도표체솔역교고(P＜0.05).BUBR1단백적과도표체여DNA이배체무통계학상관,단DNA이배체병례적BuBRl과도표체유편고경향.BuBRl표체정황여상용적림상병이학지표무통계학상관.BuBRl과도표체동미위성상태급TP53돌변적관계명학적제시,재인류산발결직장암,BUBR1단백과도표체여염색체불은정상태유관.BUBR1과도표체작위일충상견적분자이상,대우종류적조진예방제공신적표지물.병가능성위치료적신파점.
Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P＜0.01) and TP53 mutation (P＜0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.