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肝细胞癌基因组DNA拷贝数变异的性别差异性
闻炳基1,丛文铭2,王爱忠3,贺松琴1,JIANGHong-mei4,董辉2,HOULi-fang5,朱忠政1*
0
(1. 解放军113医院肿瘤科, 宁波 315040
2. 第二军医大学东方肝胆外科医院病理科, 上海 200438
3. 解放军113医院病理科, 宁波 315040
4. Department of Statistics, Northwestern University, Evanston, IL 60208, USA
5. Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
*通信作者)
摘要:
目的 比较男性与女性肝细胞癌(HCC)在基因组DNA拷贝数变异(CNA)方面的差异性。方法 采用高分辨率微阵列比较基因组杂交技术(array-CGH)检测 17例女性与46例男性HCC患者的CNA差异。结果 女性HCC染色体片段1q21.3-q22扩增频率(76.5% vs 37.0%,P=0.009)、11q11扩增频率(35.3% vs 0.0%,P=0.000 2)、19q13.31-q13.32扩增频率(23.5% vs 0.0%,P=0.004)和16p11.2丢失频率(35.3% vs 6.5%,P=0.009)显著高于男性,而男性则有更高频率的11q11丢失(63.0% vs 17.6%,P=0.002)。进一步统计分析结果 显示,11q11扩增与19q13.31-q13.32扩增(P=0.042)及16p11.2丢失(P=0.033)显著相关,而1q21.3-q22扩增与19q13.31-q13.32扩增(P=0.046)显著相关。结论 CNA在性别特异性HCC演进过程中可能发挥重要作用。
关键词:  微阵列比较基因组杂交  拷贝数变异  性别分布  肝肿瘤
DOI:10.3724/SP.J.1008.2012.05
投稿时间:2011-10-24修订日期:2011-11-26
基金项目:国家自然科学基金(30470791),南京军区医学科技创新基金(08MA023,09MA043),宁波市自然科学基金(2009A610126).
Sex-dependent differences in DNA copy number alterations in hepatocellular carcinoma
WEN Bing-ji1,CONG Wen-ming2,WANG Ai-zhong3,HE Song-qin1,JIANG Hong-mei4,DONG Hui2,HOU Li-fang5,ZHU Zhong-zheng1*
(1. Department of Oncology, No.113 Hospital of PLA, Ningbo 315040, Zhejiang, China
2. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
3. Department of Pathology, No.113 Hospital of PLA, Ningbo 315040, Zhejiang, China
4. Department of Statistics, Northwestern University, Evanston, IL 60208, USA
5. Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
*Corresponding author.)
Abstract:
Objective To identify the sex-related DNA copy number alterations(CNA) in hepatocellular carcinoma(HCC). MethodsHigh-resolution array comparative genomic hybridization(array-CGH) was used to examine 17 female and 46 male HCCs. Two-tailed Fisher’s exact test or χ2 test was used to compare the differences in CNA between females and males. ResultsThe overall frequencies and patterns of CNA in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to male on 1q21.3-q22(76.5% vs 37.0%, P=0.009), 11q11(35.3% vs 0.0%, P=0.000 2) and 19q13.31-q13.32(23.5% vs 0.0%, P=0.004), and more loss on 16p11.2(35.3% vs 6.5%, P=0.009). Relative to females, male cases had more copy number loss on 11q11(63.0% vs 17.6%, P=0.002). Further analyses showed that 11q11 gain was correlated with 19q13.31-q13.32 gain(P=0.042) and 16p11.2 loss(P=0.033), while 1q21.3-q22 gain was correlated with 19q13.31-q13.32 gain(P=0.046). ConclusionOur findings suggest that CNA may play an important role in sex-related difference in HCC development.
Key words:  array comparative genomic hybridization  copy number alteration  sex distribution  liver neoplasms