Objective To investigate genetic changes in individuals that may influence development of hepatocellular carcinoma (HCC)associated with hepatitis B virus (HBV)and exposure to aflatoxin B1 (AFB1). Method Patients with HCC were divided into four groups based on HBV infection and AFB1 exposure status:HBV(+)/AFB1(+),n=10;HBV(+)/AFB1(-),n=10;HBV(-)/AFB1(+), n=6;HBV(-)/AFB1(-),n=6.Array-based comparative genomic hybridization(Array CGH)was carried out on tumor tissue to identify genome-wide genetic changes. Result Among all 32 tissue samples,573 CNAs were identified,comprising 184 gains and 389 losses. Frequent gains were observed in the following regions:1q,4p,5p,6p,7p,8q,10p,17q,20p,20q and X.Frequent losses were observed in the following regions:1p,2q,4q,8p,9p,10q,11q,13q,14q,16p,16q,17p,19p,19q,21q,22q and Y.A total of 25 RARs were de-tected:8 RAR gains were 1q21.1-q44,5p13.2-p15.3,6p12.1-p25.2,7q21.1-q35,8q11.2-q24.3,17q12-q25.2,18q12.3-q22.3 and X;17 RARs losses were 1p31.1-p36.2,2q23.2-q37.2,4q12-q35.2,6q14.1-q26,8p12-p23.2,9p21.1-p24.2,10q21.3-q26.2,13q12.1-q21.1, 14q21.3-q32.2,16p12.1-p13.2,16q12.1-q24.1,17p12-p13.3,19p13.1-p13.3,19q13.2-q13.4,21q21.3-q22.2,22q11.2-q13.2 and Y.Loss of 8p12-p23.2 was associated with higher TNM tumor stage(TNM I-II:38.9% vs TNM Ⅲ:92.9%;P=0.038)and shorter tumor-free survival(P=0.045).Loss of 4q13.3-q35.2 and 13q12.1-q21.2 and gain of 7q11.2-q35 occurred at higher frequency among HBV(+)/AFB1(+)patients than among the other groups. Univariate analysis found tumor-free survival to be associated with tumor size,serum AFP,BCLC,TNM stage,invasion and metastasis,and loss of 8p12-p23.2(all P<0.05).Multivariate analysis revealed three of these fac-tors to be independently associated with tumor-free survival:serum AFP(≥400),TNM stage,and loss of 8p12-p23.2(all P≤0.045). Conclusion Several chromosomal alterations were identified in the genomes of individuals with HCC in Guangxi.Loss of 19p13.1-p13.3 may be a characteristic feature of the disease in this part of China. Loss of 8p12-p23.2 may occur later during HCC progression and is associated with shorter tumor-free survival. Loss of 4q12-q35.2 and 13q12.1-q21.1 and gain of 7q21.1-q35 may be associated with the synergistic hepatocarcinogenic effect of HBV infection combined with AFB1 exposure.%目的：研究乙肝病毒/黄曲霉毒素B1双暴露相关性肝细胞性肝癌（hepatocellular carcinoma，HCC）染色体遗传学畸变的特点。方法将32例手术切除经病理证实为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组为HBV（+）/AFB1（+）10例；B组为HBV（+）/AFB1（-）10例；C组为HBV（-）/AFB1（+）6例；D组为HBV（-）/AFB1（-）6例。应用微阵列比较基因组杂交技术（Array CGH）检测分析其22对染色体DNA拷贝数的变化。结果32例HCC样本中，共发现573个染色体畸变区段（chromosomal aberrations，CNAs）。其中1q、4p、5p、6p、7p、8q、10p、17q、20p、20q和X主要表现为扩增区段；1p、2q、4q、8p、9p、10q、11q、13q、14q、16p、16q、17p、19p、19q、21q、22q和Y主要表现为缺失区段。同时，共检测出25个染色体发生高频畸变的区段（recurrently altered regions，RARs)，其中1q21.1-q44、5p13.2-p15.3、6p12.1-p25.2、7q11.2-q35、8q11.2-q24.3、17q12-q25.2、18q12.3-q22.3和 X 为高频率扩增区段，而1p31.1-p36.2、2q23.2-q37.2、4q12-q35.2、6q14.1-q26、8p12-p23.2、9p21.1-p24.2、10q21.3-q26.2、13q12.1-q21.1、14q21.3-q32.2、16p12.1-p13.2、16q12.1-q24.1、17p12-p13.3、19p13.1-p13.3、19q13.2-q13.4、21q21.3-q22.2、22q11.2-q13.2和Y染色体为高频缺失区段。8p12-p23.2缺失的发生率在进展期HCC(TNM分期为Ⅲ~Ⅳ期)中明显高于早期HCC (TNM分期为I~II期)（P=0.038）。4q12-q35.2、13q12.1-q21.1的缺失及7q21.1-q35的扩增发生率在A组中最高。Cox模型分析结果示：在单因素分析中AFP水平、肿瘤大小、TNM分期、BCLC分期、侵袭与转移的发生、8p12-p23.2的缺失以及19p13.1-p13.3的缺失等为影响患者无瘤生存时间的危险因素（P<0.05）。而在多因素分析中AFP水平、TNM分期以及8p12-p23.2的缺失等为影响患者无瘤生存时间的危险因素（P<0.05）。结论广西地区HCC染色体遗传学改变具有多样性，其中染色体19p13.1-p13.3的高频缺失可能为广西地区HCC特有的分子生物学特征之一。染色体8p12-p23.2的缺失可能为HCC的晚期事件，并且与患者的不良预后有关。染色体4q12-q35.2、13q12.1-q21.1缺失及7q21.1-q35扩增可能与HBV/AFB1双因素的协同致癌作用有关。
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