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http://dx.doi.org/10.7314/APJCP.2012.13.1.225

Sex-related Differences in DNA Copy Number Alterations in Hepatitis B Virus-Associated Hepatocellular Carcinoma  

Zhu, Zhong-Zheng (Department of Oncology, No. 113 Hospital of People's Liberation Army)
Wang, Dong (Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University)
Cong, Wen-Ming (Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)
Jiang, Hongmei (Department of Statistics, Northwestern University)
Yu, Yue (Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University)
Wen, Bing-Ji (Department of Oncology, No. 113 Hospital of People's Liberation Army)
Dong, Hui (Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)
Zhang, Xiao (Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University)
Liu, Shu-Fang (Parexel International)
Wang, Ai-Zhong (Department of Pathology, No. 113 Hospital of People's Liberation Army)
Zhu, Guanshan (Innovation Center China of AstraZeneca R&D)
Hou, Lifang (Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.1, 2012 , pp. 225-229 More about this Journal
Abstract
Background: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. Methods: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher's exact or ${\chi}^2$ tests was used to compare CNAs between females and males. Results: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). Conclusions: These findings suggest that CNAs may play a role in sex-related differences in HBVassociated HCC development.
Keywords
Array comparative genomic hybridization; copy number alteration; hepatocellular carcinoma; sex;
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1 Wands J (2007). Hepatocellular carcinoma and sex. N Engl J Med, 357, 1974-6.   DOI
2 Wei XL, Xu H, Kufe D (2006). MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Molecular Cell, 21, 295-305.   DOI
3 Wong N, Chan A, Lee SW, et al (2003). Positional mapping for amplified DNA sequences on 1q21-q22 in hepatocellular carcinoma indicates candidate genes over-expression. J Hepatol, 38, 298-306.   DOI
4 Wong N, Lai P, Lee SW, et al (1999). Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis - Relationship to disease stage, tumor size, and cirrhosis. Am J Pathol, 154, 37-43.   DOI
5 Wong N, Lai P, Pang E, et al (2000). Genomic aberrations in human hepatocellular carcinomas of differing etiologies. Clin Cancer Res, 6, 4000-9.
6 Woo HG, Park ES, Lee JS, et al (2009). Identification of potential driver genes in human liver carcinoma by genomewide screening. Cancer Res, 69, 4059-66.
7 Yeh SH, Chen PJ (2010). Gender disparity of hepatocellular carcinoma: the roles of sex hormones. Oncology, 78, 172-9.
8 Yu MW, Chen CJ (1993). Elevated serum testosterone levels and risk of hepatocellular carcinoma. Cancer Res, 53, 790-4.
9 Zondervan PE, Wink J, Alers JC, et al (2000). Molecular cytogenetic evaluation of virus-associated and non-viral hepatocellular carcinoma: analysis of 26 carcinomas and 12 concurrent dysplasias. J Pathol, 192, 207-15.   DOI
10 Raidl M, Pirker C, Schulte-Hermann R, et al (2004). Multiple chromosomal abnormalities in human liver (pre)neoplasia. J Hepatol, 40, 660-8.   DOI
11 Rashid A, Wang JS, Qian GS, et al (1999). Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations. Brit J Cancer, 80, 59-66.   DOI
12 Rudolph KL, Chang S, Millard M, Schreiber-Agus N, DePinho RA (2000). Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery. Science, 287, 1253-8.   DOI
13 Slovak ML, Bedell V, Hsu YH, et al (2011). Molecular Karyotypes of Hodgkin and Reed-Sternberg Cells at Disease Onset Reveal Distinct Copy Number Alterations in Chemosensitive versus Refractory Hodgkin Lymphoma. Clin Cancer Res, 17, 3443-54.   DOI
14 Sy SM, Wong N, Mok TS, et al (2003). Genetic alterations of lung adenocarcinoma in relation to smoking and ethnicity. Lung Cancer, 41, 91-9.   DOI
15 Takemoto N, Iizuka N, Yamada-Okabe H, et al (2005). Sex-based molecular profiling of hepatitis C virus-related hepatocellular carcinoma. Int J Oncol, 26, 673-8.
16 Tornillo L, Carafa V, Sauter G, et al (2002). Chromosomal alterations in hepatocellular nodules by comparative genomic hybridization: high-grade dysplastic nodules represent early stages of hepatocellular carcinoma. Lab Invest, 82, 547-53.   DOI
17 Terracciano L, Tornillo L (2003). Cytogenetic alterations in liver cell tumors as detected by comparative genomic hybridization. Pathologica, 95, 71-82.
18 Terris B, Ingster O, Rubbia L, et al (1997). Interphase cytogenetic analysis reveals numerical chromosome aberrations in large liver cell dysplasia. J Hepatol, 27, 313-9.   DOI
19 Thompson SL, Bakhoum SF, Compton DA (2010). Mechanisms of chromosomal instability. Curr Biol, 20, R285-95.   DOI
20 Venkatraman ES, Olshen AB (2007). A faster circular binary segmentation algorithm for the analysis of array CGH data. Bioinformatics, 23, 657-63.   DOI
21 Maldonado V, Espinosa M, Pruefer F, et al (2010). Gene regulation by BCL3 in a cervical cancer cell line. Folia Biol (Praha), 56, 183-93.
22 Marchio A, Meddeb M, Pineau P, et al (1997). Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer, 18, 59-65.   DOI
23 Massion PP, Zou Y, Chen H, et al (2008). Smoking-related genomic signatures in non-small cell lung cancer. Am J Respir Crit Care Med, 178, 1164-72.   DOI
24 Midorikawa Y, Tang W, Sugiyama Y (2007). High-resolution mapping of copy number aberrations and identification of target genes in hepatocellular carcinoma. Biosci Trends, 1, 26-32.
25 Midorikawa Y, Tsutsumi S, Nishimura K, et al (2004). Distinct chromosomal bias of gene expression signatures in the progression of hepatocellular carcinoma. Cancer Res, 64, 7263-70.   DOI
26 Olshen AB, Venkatraman ES, Lucito R, Wigler M (2004). Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics, 5, 557-72.   DOI
27 Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM (2009). Pathogenesis of hepatocellular carcinoma and molecular therapies. Curr Opin Gastroenterol, 25, 186-94   DOI
28 Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P (2005). Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. Br J Cancer, 92, 935-41.   DOI
29 Naugler WE, Sakurai T, Kim S, et al (2007). Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science, 317, 121-4.   DOI
30 Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.   DOI
31 Pinkel D, Albertson DG (2005). Array comparative genomic hybridization and its applications in cancer. Nat Genet, 37 Suppl, S11-7   DOI
32 Barrett MT, Scheffer A, Ben-Dor A, et al (2004). Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA. Proc Natl Acad Sci USA, 101, 17765-70.   DOI
33 Guan XY, Fang Y, Sham JST, et al (2001). Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization. (vol 29, pg 110, 2000). Gene Chromosome Cancer, 30, 110-?.   DOI
34 Baudis M (2007). Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data. BMC Cancer, 7, 226.   DOI
35 Drewniok C, Wienrich BG, Schon M, et al (2004). Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer. Arch Dermatol Res, 296, 59-66.   DOI
36 El-Serag HB, Rudolph KL (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132, 2557-76.   DOI
37 Kuiper RP, Ligtenberg MJ, Hoogerbrugge N, Geurts van Kessel A (2010). Germline copy number variation and cancer risk. Curr Opin Genet Dev, 20, 282-9.   DOI
38 Laurent-Puig P, Legoix P, Bluteau O, et al (2001). Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology, 120, 1763-73.   DOI
39 Lee SA, Ho C, Roy R, et al (2008). Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer. Hepatology, 47, 1200-10.   DOI