广西地区乙肝病毒/黄曲霉毒素双暴露因素下肝细胞癌染色体遗传学改变的初步研究

目的 探讨广西地区人群乙肝病毒/黄曲霉毒素(HBV/AFB1)双暴露相关性肝细胞癌(HCC)染色体遗传学改变的特点.方法 32例HCC的癌组织,运用微阵列比较基因组杂交技术(Array CGH)检测其22对染色体的变化.结果 (1)32例HCC中,大部分的染色体拷贝数都有不同程度的变化.发生扩增的区段有1 q、7q、8q,其中1q、8q为高频扩增区段.发生缺失区段有1 p、4q、8p、9p、13q、14q、16p、16q、17p、18q、19p、Y,其中1p、4q、8p、16q、17p、19p为高频缺失区段；(2)同时,还存在着若干DNA拷贝数扩增或缺失的小区段.缺失显著的小区段有:2p25.1-p25.2、3q22.3-q23、7p14.1-p14.3.扩增显著的小区段有:9p13.2-9p21;(3)聚类分析发现:13q缺失发生率在HBsAg(+)/AFB1(+)、HBsAg(+)/AFB1(-)、HBsAg(-)/AFB1(+)、HBsAg(-)/AFB1(-)4个亚组中呈依次递减(x2=6.452,P＜0.05).4p在HBsAg(+)/AFB1(-)组中以扩增为主,而在HBsAg(-)/AFB1(+)组与HBsAg(-)/AFB1(-)组则以缺失为主.19q在HBsAg(+)/AFB1(+)组中以扩增为主,在HBsAg(-)/AFB1(+)组与HBsAg(-)/AFB1(-)组中以缺失为主.结论 广西地区肝癌染色体遗传学改变具有多样性,其中19p、2p25.1-25.2、3q22.3-q23的缺失及9p13.2-9p21的扩增可能为该地区肝癌特有的遗传学特征之一.13q的缺失可能与该地区乙肝病毒/黄曲霉毒素双因素的协同作用有关.

Chromosome genetic changes in hepatocellular carcinoma with double exposure to hepatitis B virus/aflatoxin B1 : A preliminary study from Guangxi

Objective To study the chromosome genetic changes in hepatocellular carcinoma (HCC) with double exposure to hepatitis B virus/aflatoxin B1 (HBV/AFB1) in Guangxi.Method Differences in genomic alterations in 32 patients with HCC were analyzed using comparative genomic hybridization(CGH).Results (1) The majority of chromosome copy number in the 32 HCC samples had varying degrees of change.The amplification of chromosome regions were 1q,7q,8q,with the high frequency regions being 1q,8q.The deletion of chromosome regions were 1p,4q,8p,9p,13q,14q,16p,16q,17p,18q,19p,Y,with the high frequency regions being 1p,4q,8p,16q,17p,19p;(2) There were also some high copy number amplification or deletion of small regions,such as 2p25.1-p25.2,3q22.3-q23,7p14.1-p14.3,and 9p13.2-9p21; (3) Hierarchical clustering analysis showed that the rate of deletion of chromosome 13q decreased progressively in the following 4 groups:-HBsAg(+)/AFB1 (+),HBsAg(+)/AFB1 (-),HBsAg( - )/AFB1 ( + ),and HBsAg( - )/AFB1 (-) (x2=6.452,P＜0.05).4p was found mainly to be amplified in the HBsAg(+)/AFB1(-)group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg( - )/AFB1(-) groups.19q was found mainly to be amplified in the HBsAg(+)/AFB1(+) group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg(-)/AFB1(-) groups.Conclusion The chromosome genetic changes of HCC in Guangxi showed multiplicity.The deletion of chromosome 19p,2p25.1-25.2,3q22.3-q23,7p14.1-p14.3 and amplification of chromosome 9p13.2-9p21 are probably unique genetic characteristics of HCC in this region.The combined effects of Hepatitis B virus and aflatoxin B1 may contribute to deletion of chromosome 13q of HCC in Guangxi.