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中国癌症防治杂志 ›› 2012, Vol. 4 ›› Issue (4): 307-310.doi: 10.3969/j.issn.1674-5671.2012.04.02

• 基础研究 • 上一篇    下一篇

乙肝病毒/黄曲霉毒素双暴露因素下肝癌13号染色体畸变以及RB1基因表达的初步研究

  

  1. 广西医科大学附属肿瘤医院肝胆外科;广西医科大学第一附属医院肝胆血管外科
  • 出版日期:2012-12-25 发布日期:2013-01-11
  • 通讯作者: 黎乐群 E-mail:li_lequn@263.net
  • 基金资助:

    国家自然科学基金资助项目(30960021);广西自然科学基金资助项目(桂科基 0640101)

Preliminary study of genetic changes on chromosome 13 and RB1 gene expression in hepatocellular carcinoma in patients exposed to both hepatitis B virus and aflatoxin B1

  • Online:2012-12-25 Published:2013-01-11

摘要: 目的 探讨乙肝病毒/黄曲霉毒素双暴露下肝细胞性肝癌(hepatocellular carcinoma,HCC)13号染色体遗传学改变的特点,以及对定位于13q14.2基因座位点抑癌基因RB1的影响。方法 32例手术切除且经病理证实为HCC的癌组织,按照乙肝病毒与黄曲霉毒素的暴露情况,分为4个亚组:A组HBV(+)/AFB1(+)10例;B组HBV(+)/AFB1(-)10例;C组 HBV(-)/AFB1(+)6例;D组HBV(-)/AFB1(-)6例。应用微阵列比较基因组杂交技术(Array CGH)检测包括13号染色体在内的23对染色体区段的变化情况,并通过RT-PCR检测RB1 mRNA的表达情况。结果 32例中有15例染色体13q14.2发生缺失,缺失率为46.9%(15/32)。13q14.2缺失的发生频率在A组、B组、C组、D组中分别为80.0%(8/10)、50.0%(5/10)、33.3%(2/6)和0%(0/6)。其中A组分别与C组、D组比较,差异具有统计学意义(P<0.05);B组与D组比较,差异亦有统计学意义(P<0.05)。RT-PCR检测显示RB1 mRNA的表达半定量灰度值在13q14.2缺失组中显著低于13q14.2无缺失组(P=0.003)。结论 染色体13q畸变在HCC中是一个常见的分子生物学事件,其中13q14.2的缺失可能与HBV和AFB1双暴露的协同作用有关,HCC中13q14.2的缺失是导致RB1基因失活的因素之一。

关键词: 肝肿瘤, 乙肝病毒, 黄曲霉毒素B1, 染色体13q14.2, RB1基因

Abstract: Objective To explore genetic changes on chromosome 13 and particularly expression of the RB1 anti-oncogene,located on 13q14.2,in hepatocellular carcinoma(HCC) in patients exposed to both hepatitis B virus(HBV) and aflatoxin B1(AFB1). Methods Thirty-two HCC tissue samples were divided into four subgroups according to HBV and AFB1 exposure:group A(n=10),HBV(+)/AFB1(+);group B(n=10),HBV(+)/AFB1(-);group C(n=6),HBV(-)/AFB1(+);group D(n=6),HBV(-)/AFB1(-). Genomewide analysis was carried out using array-based comparative genomic hybridization(aCGH),and RT-PCR was used to detect RB1 mRNA expression. Results Deletion of 13q14.2 was found in 15 of 32(46.9%) samples overall,and deletion rates in each group were as follows: group A,80.0%(8/10);group B,50.0%(5/10);group C,33.3%(2/6);and group D,0%(0/6).Deletion rates differed significantly between groups A and C,A and D,and B and D(all P<0.05).RB1 mRNA expression was lower in the 15 cases with the 13q14.2 deletion than in the 17 cases possessing 13q14.2. Conclusions Genetic 13q14.2,are frequent molecular characteristics of HCC.Deletion of 13q14.2 may result from the synergistic effects of HBV and AFB1,and it may contribute to RB1 gene inactivation in HCC.

Key words: Liver neoplasms, Hepatitis B Virus (HBV), Aflatoxin B1, Chromosome 13q14.2, RB1 gene