Copy number increase of HER-2 in colorectal cancers

Xiong,Yi; Fang,Zhengyu; Zhang,Chao; Qi,Guolong; Liu,Wenli; Zhang,Wei; Wan,Jun

doi:10.3892/ol.2010.225

Copy number increase of HER-2 in colorectal cancers

Authors:
- Yi Xiong
- Zhengyu Fang
- Chao Zhang
- Guolong Qi
- Wenli Liu
- Wei Zhang
- Jun Wan
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Affiliations: Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, Guangdong, P.R. China, Department of Medical Information, Medical Collage of Jinan University, Guangzhou, P.R. China, JNU-HKUST Joint Lab, Ji-Nan University, Guangdong, P.R. China
Published online on: December 8, 2010 https://doi.org/10.3892/ol.2010.225
Pages: 331-335

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Abstract

HER-2 is involved in genetic instability and is overexpressed in a number of human carcinomas, including colorectal cancer (CRC). The choromosomal locus of HER-2, 17q21, is frequently amplified in breast cancer, but the correlation between copy-number variations and HER-2 overexpression in CRC has yet to be elucidated. The functional impact of such regions requires extensive investigation in large numbers of CRC samples. Case-matched tissues of colorectal adenocarcinomas and adjacent normal epithelia (n=134) were included in this study. Quantitative PCR was performed to examine the copy number and mRNA expression of HER-2 in CRC. The results showed that copy number gains of HER-2 were detected in a relatively high percentage of CRC samples (35.1%, 47 out of 134). A positive correlation was noted between the copy number increase of HER-2 and tumor progression. Furthermore, copy number gains of HER-2 showed a positive correlation with mRNA overexpression in CRC. However, the expression levels of HER-2 mRNA were also enhanced in the group of CRC samples with unaltered copy numbers. In conclusion, the findings suggest that a copy number increase of HER-2 is a potential diagnostic indicator for CRC; whether alone or in combination with other markers.

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1	Schechter AL, Stern DF, Vaidyanathan L, et al: The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 312:513–516. 1984. View Article : Google Scholar : PubMed/NCBI
2	Prenzel N, Fischer OM, Streit S, Hart S and Ullrich A: The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer. 8:11–31. 2001. View Article : Google Scholar : PubMed/NCBI
3	Siddiqa A, Long LM, Li L, Marciniak RA and Kazhdan I: Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins Survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways. BMC Cancer. 8:1292008. View Article : Google Scholar : PubMed/NCBI
4	Pohl M, Stricker I, Schoeneck A, et al: Antitumor activity of the HER2 dimerization inhibitor pertuzumab on human colon cancer cells in vitro and in vivo. J Cancer Res Clin Oncol. 135:1377–1386. 2009. View Article : Google Scholar : PubMed/NCBI
5	Al-Kuraya K, Novotny H, Bavi P, et al: HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer. J Clin Pathol. 60:768–772. 2007. View Article : Google Scholar : PubMed/NCBI
6	Herreros-Villanueva M, Rodrigo M, Claver M, et al: KRAS, BRAF, EGFR and HER2 gene status in a Spanish population of colorectal cancer. Mol Biol Rep. June;2010.(E-pub ahead of print).
7	Yamashita H, Nishio M, Toyama T, et al: Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res. 6:R24–R30. 2004. View Article : Google Scholar : PubMed/NCBI
8	Leonard DS, Hill AD, Kelly L, Dijkstra B, McDermott E and O'Higgins NJ: Anti-human epidermal growth factor receptor 2 monoclonal antibody therapy for breast cancer. Br J Surg. 89:262–271. 2002. View Article : Google Scholar : PubMed/NCBI
9	Sung JJ, Lau JY, Goh KL and Leung WK: Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 6:871–876. 2005. View Article : Google Scholar : PubMed/NCBI
10	Lu JB, Sun XB, Dai DX, et al: Epidemiology of gastroenterologic cancer in Henan Province, China. World J Gastroenterol. 9:2400–2403. 2003.PubMed/NCBI
11	Lichtenstein P, Holm NV, Verkasalo PK, et al: Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 343:78–85. 2000.
12	Andrews J, Kennette W, Pilon J, et al: Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number. PLoS One. 5:e86652010. View Article : Google Scholar : PubMed/NCBI
13	Cho EK, Tchinda J, Freeman JL, Chung YJ, Cai WW and Lee C: Array-based comparative genomic hybridization and copy number variation in cancer research. Cytogenet Genome Res. 115:262–272. 2006. View Article : Google Scholar : PubMed/NCBI
14	Orsetti B, Courjal F, Cuny M, Rodriguez C and Theillet C: 17q21–q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification. Oncogene. 18:6262–6270. 1999.
15	Buness A, Kuner R, Ruschhaupt M, Poustka A, Sultmann H and Tresch A: Identification of aberrant chromosomal regions from gene expression microarray studies applied to human breast cancer. Bioinformatics. 23:2273–2280. 2007. View Article : Google Scholar : PubMed/NCBI
16	Yao J, Weremowicz S, Feng B, et al: Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression. Cancer Res. 66:4065–4078. 2006. View Article : Google Scholar : PubMed/NCBI
17	Benusiglio PR, Pharoah PD, Smith PL, et al: HapMap-based study of the 17q21 ERBB2 amplicon in susceptibility to breast cancer. Br J Cancer. 95:1689–1695. 2006. View Article : Google Scholar : PubMed/NCBI
18	Dear PH: Copy-number variation: the end of the human genome? Trends Biotechnol. 27:448–454. 2009. View Article : Google Scholar : PubMed/NCBI
19	Shlien A, Tabori U, Marshall CR, et al: Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci USA. 105:11264–11269. 2008. View Article : Google Scholar : PubMed/NCBI
20	Divne AM and Allen M: A DNA microarray system for forensic SNP analysis. Forensic Sci Int. 154:111–121. 2005. View Article : Google Scholar : PubMed/NCBI
21	Macconaill LE, Aldred MA, Lu X and Laframboise T: Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation. BMC Genomics. 8:2112007. View Article : Google Scholar : PubMed/NCBI
22	Gorringe KL and Campbell IG: High-resolution copy number arrays in cancer and the problem of normal genome copy number variation. Genes Chromosomes Cancer. 47:933–938. 2008. View Article : Google Scholar : PubMed/NCBI
23	Mitra A, Liu G and Song J: A genome-wide analysis of array-based comparative genomic hybridization (CGH) data to detect intra-species variations and evolutionary relationships. PLoS One. 4:e79782009. View Article : Google Scholar
24	Malan V, Chevallier S, Soler G, et al: Array-based comparative genomic hybridization identifies a high frequency of copy number variations in patients with syndromic overgrowth. Eur J Hum Genet. 18:227–232. 2010. View Article : Google Scholar : PubMed/NCBI
25	Dermitzakis ET and Stranger BE: Genetic variation in human gene expression. Mamm Genome. 17:503–508. 2006. View Article : Google Scholar : PubMed/NCBI
26	Guryev V, Saar K, Adamovic T, et al: Distribution and functional impact of DNA copy number variation in the rat. Nat Genet. 40:538–545. 2008. View Article : Google Scholar : PubMed/NCBI
27	Henrichsen CN, Vinckenbosch N, Zollner S, et al: Segmental copy number variation shapes tissue transcriptomes. Nat Genet. 41:424–429. 2009. View Article : Google Scholar : PubMed/NCBI
28	Sexton T, Umlauf D, Kurukuti S and Fraser P: The role of transcription factories in large-scale structure and dynamics of interphase chromatin. Semin Cell Dev Biol. 18:691–697. 2007. View Article : Google Scholar : PubMed/NCBI