【作者】 康雪玲；

【导师】 李锋；

【作者基本信息】 石河子大学 ， 病理学与病理生理学， 2009， 硕士

【摘要】 目的:运用比较基因组杂交技术(CGH)分析肾细胞癌的染色体基因组变化特征,并比较不同组织学亚型、分级以及不同临床分期的肾细胞癌之间的基因组变化差异及意义。方法:选用外科手术切除并经病理组织学证实的46例原发性肾细胞癌(其中透明细胞癌10例,乳头状肾细胞癌13例,嫌色细胞癌12例,Xp11.2易位/TFE3基因融合相关性肾癌9例,未分化癌2例)石蜡包埋组织,应用CGH技术分析肾细胞癌基因组的变化;并比较不同组织学亚型、分级和临床分期的肾细胞癌之间基因组变化差异。所有数据资料均运用SPSS 13.0软件包进行统计学分析。结果:CGH分析结果显示:1. 46例肾细胞癌染色体基因组均存在不同程度的变化,其中扩增最常见于7q(47.8%),16p(39.1%),20q(34.8%) ,最常累及的染色体区段为7q22-31(39.1%)16p 12-13(21.7%),20q12-13(21.7%) ;而缺失最常见的是1p(45.7%),3p(45.7%),13q(37.0%),14q(30.4), 8p(30.4%),最常累及的染色体区段为3p22(21.7%), 8p16-23(26.1%),14q22-32(26.1%)。2.不同亚型肾细胞癌染色体基因组的变化各具特点:(1) 10例透明细胞癌中,扩增最常见的是7q(90%),16p(80%),5q (60%),缺失最常见的是3p(90%),8p(80%),1p(70%),4p(60%),4q(60%),9p(60%);(2) 13例乳头状癌中,扩增最常见的是7p(61.5%),7q(61.5%),12q(61.5%),16q(53.8%), 20p(53.8%),20q(53.8%),缺失最常见的是14q(61.5%),18q(61.5%),13q(53.8%),3p(46.2%),4p(46.2%),6q(46.2%);(3) 12例嫌色细胞癌中,扩增最常见的是1q(58.3%),3q(50%),1p(41.7%),缺失最常见的是1p(66.7%),17p(66.7%),10p(58.3%),13p(5 8.3%),2q(50%),8p(50%)。1q21-23扩增多见于嫌色细胞癌肉瘤样变,与非肉瘤样变嫌色细胞癌具有显著差异(P=0.010);(4) 9例Xp11.2易位/TFE3基因融合相关性肾癌中,扩增最常见的是Xp (66.7%),7q(55.6%),12q(55.6%),8p(44.4%),8q(44.4%),16q(44.4%),17p(44.4%),17q(44.4%),20q(44.4%) ,缺失最常见的是3p(44.4%),9q(44.4%),14q(44.4%);(5) 2例未分化癌中,扩增最常见1p,1q,3q,8p,16q,缺失最常见的是2p,2q,3p, 5p,6p,11q,17p,17q,20p。3.在不同临床TNM分期中,5q及7q扩增多见于Ⅰ～Ⅱ期患者,与Ⅲ～Ⅳ期肾细胞癌患者间有显著差异(P=0.002和P=0.007);20q扩增及9q缺失多见于Ⅲ～Ⅳ期患者,与Ⅰ～Ⅱ期肾细胞癌患者间有显著差异(P=0.002和P=0.001)。4. 7q扩增在透明细胞癌与乳头状癌1-2级(Fuhrman核型分级系统)中高频发生,与3-4级者差异显著(P=0.045)。结论:(1)染色体7q,16p,20q扩增及1p,3p,13q,14q,8p缺失与肾细胞癌发生有相关性。(2)5q和7q扩增可能提示肾细胞癌预后较好,20q扩增与9q缺失可能提示肾细胞癌预后较差。(3)7q扩增与低级别透明细胞癌及乳头肾癌相关,提示与预后有关。更多还原

【Abstract】 Objective: To characterize the profiles of chromosome imbalance of renal cell carcinoma by Comparative Genomic Hybridization (CGH).And compare the different alterations among the histological subtypes , grading and clinical staging.Methods: Forty-six primary renal cell carcinoma for which formalin-fixed, paraffin-embedded samples were available were collected from the archives of the Department of Pathology. Including10 clear cell renal cell carcinoma cases, 13 papillary renal cell carcinoma cases, 12 chromophobe renal cell carcinoma cases, 9 renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions cases, and 2 undifferentiated renal carcinoma cases were collected for the study. A set of representative hematoxylin and eosin stained slides were marked with identifying numbers and reviewed individually by two pathologists blinded to all clinical information according to 2004 WHO Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs.We screened DNA copy number changes in whole genomes by CGH in 46 primary renal cell carcinoma. Analyse according to histological type, grading,clinical staging, respectively. All data were analyzed using the SPSS 13.0 software package.Results: 1. 46 cases with renal cell carcinoma showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. The frequently gained chromosome arms of RCC were 7q,16p,20q, and the frequently lost chromosome arms of RCC were 1p,3p,13q,14q,8p. 2. Different histological type of RCC showed different abnormality of DNA copy number. (1) The frequently gained chromosome arms of CCRCC were 7q,16p,5q; the frequently lost chromosome arms were 3p,8p,1p, 4p,4q,9p. (2) The frequently gained chromosome arms of PRCC were 7p,7q,12q,16q,20p,20q; the frequently lost chromosome arms were 14q,18q,13q,3p,4p,6q. (3) The frequently gained chromosome arms of ChrRCC were 1q,3q,1p; the frequently lost chromosome arms were1p,17p,10p,13p,2q,8p. Gains of 1q21-23 significantly correlated with ChrRCC and sarcomatoid variants ChrRCC type (P=0.010). (4) The frequently gained chromosome arms of Xp11.2RCC were Xp,7q,12q,8p,8q,16q,17p,17q,20q; the frequently lost chromosome arms were3p, 9q,14q. (5) The frequently gained chromosome arms of UnRCC were 1p,1q,3q,8p,16q; the frequently lost chromosome arms were2p,2q,3p,5p,6p,11q,17p,17q,20p. 3. Gains of 5q,7q,20q and losses of 9q were significantly correlated with clinical staging (P=0.002, P=0.007). 4. 7q was frequently gained in grade 1-2 than 3-4 (nuclear grade of Fuhrman system) of CCRCC and PRCC (P=0.045).Conclusions:(1)7q,16p,2Qq gained and 1 p,3p,13q,14q,8p losses are correlated with RCC. (2) gains of Sq and 7q may indicated prognosis of RCC be favourable; gains of 20q and losses of 9q Enay indicated poor prognosis of RCC.(3)gains of 7q is correkated with low grade of CCRCC and PRCC,and indicated be correlated with prognosis.更多还原