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肝癌染色体DNA拷贝数的变化及其与临床病理和预后的关系 被引量:5

The change of chromosome DNA copies is associate to clinic pathology and prognosis of hepatocellular carcinoma
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摘要 目的:探讨人肝癌染色体DNA 的丢失和增加的状态及其在肝癌临床病理及预后中的意义,并为寻找肝癌相关基因提供线索。方法:收集手术切除的肝癌标本31 例,采用比较基因组杂交方法对肝癌染色体DNA 拷贝数进行检测,同时进行病理观察和随访。结果:在染色体DNA 拷贝数的增加中,以1q 的频率最高(83-9% ) ,其次为8q(61-3% ) ;在染色体DNA 的拷贝数的减少中,以16q 的频率最高(77-4 % ) ,其次为17p(61-3 % ) 和4q(51-6 % ) 。经统计分析发现,在1q 拷贝数增加的病例中,其半年生存的相对机率比无1q 扩增的病例高10-5 倍( 回归系数β= 2-35,P< 0-05) ; 有17p 丢失患者的半年内复发的相对危险性比无17p 丢失的患者高6-86 倍( 回归系数β= 1-93 , P<0-05) 。此外,1q 的增加与肿瘤大小、有无包膜、坏死程度和AFP 浓度等均呈负相关;4q 和17p 的丢失与肿瘤分化程度均呈负相关;4q 的丢失与8q 的增加呈负相关。这是第一次报道肝癌染色体DNA 拷贝数的变化与肝癌临床、病理以及预后之间的关系。结论:在肝癌的发生发展中多个染色体的DNA 拷贝数存在着高频率的变化,其中1? Objective:To explore the change of copy number of chromosomal regions of hepatocellular carcinoma(HCC) and its relationship with the clinic pathology as well as the prognosis of HCC, providing the clue of cloning the key gene in HCC. Methods:Thirty one HCC specimens obtained from surgical resection were used for detection of variation of chromosome DNA by comparative genomic hybridization. The samples also were examined pathologically and the data of follow up were collected. Results:Among the gains of chromosome DNA copies, the highest frequency was 1q (83 9%), the second highest was 8q(61 3%); Among the losses of chromosome DNA copies, the highest frequence is 16q(77 4%), the followed were 17p(61 3%) and 4q(51 6%). Multiple Logistic Regression analysis showed that six month survive relative rate of patients with 1q gain was 10 5 fold higher than that of patients without 1q gain(β=2 35,P< 0 05);the relative risk of six month recurrence of patients with 17p loss was 6 86 fold higher that of than patients without 17p loss(β=1 93,P< 0 05). Correlation analysis show that the 1q gain was negatively correlative to tumor size, capsule, necrosis degree and AFP concentration. The losses of 4q and 17p were positively correlative to tumor differentiation degree. There was positive correlation between the 4q loss and 8q gain. The 4q loss was detected in most tumors originating from sixth segment of liver and rare observed in tumors occurring in third segment of liver. This study was the first analysis of the relationship between the change of copy number of chromosomal regions and the clinic pathology as well as prognosis of HCC. Conclusions:The changes of copy number of chromosomal regions played important role during the development of HCC, and the 1q gain was a marker of good prognosis of HCC and 17p loss was a marker of poor prognosis of HCC.
出处 《癌症》 SCIE CAS CSCD 北大核心 1999年第5期509-513,共5页 Chinese Journal of Cancer
基金 国家自然科学基金!项目( 批准号39670814) 资助
关键词 肝肿瘤 染色体 DNA DNA拷贝数 Liver neoplasm Chromosomes human Prognosis Comparative Genome Hybridization
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参考文献4

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同被引文献24

  • 1Sze-hangLAU Xin-yuanGUAN.Cytogenetic and molecular genetic alterations in hepatocellular carcinoma[J].Acta Pharmacologica Sinica,2005,26(6):659-665. 被引量:7
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  • 6Knosel T,Petersen S,Schwabe H,et al.Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases[J].Virchows Arch,2002,440(2): 187-194.
  • 7Alers JC,Krijtenburg pJ,Vis AN.Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies: early cancers may contain aggressive genetic features[J].Am J Pathol,2001,158(2): 399-406.
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  • 10Lui WO,Tanenbaum DM,Larsson C.High level amplification of 1p32-33 and 2p22-24 in small cell lung carcinomas[J].Int J Oncol,2001,19(3): 451-457.

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