High-resolution detection of recurrent aberrations in lung adenocarcinomas by array comparative genomic hybridization and expression analysis of selective genes by quantitative PCR

Zhu,Hong; Wong,Maria Pik; Tin,Vicky

doi:10.3892/ijo.2014.2384

High-resolution detection of recurrent aberrations in lung adenocarcinomas by array comparative genomic hybridization and expression analysis of selective genes by quantitative PCR

Authors:
- Hong Zhu
- Maria Pik Wong
- Vicky Tin
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Affiliations: Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Pathology, The University of Hong Kong, Hong Kong, SAR, P.R. China
Published online on: April 11, 2014 https://doi.org/10.3892/ijo.2014.2384
Pages: 2068-2076

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Abstract

Genomic abnormalities are the hallmark of cancers and may harbor potential candidate genes important for cancer development and progression. We performed array comparative genomic hybridization (array CGH) on 36 cases of primary lung adenocarcinoma (AD) using an array containing 2621 BAC or PAC clones spanning the genome at an average interval of 1 Mb. Array CGH identified the commonest aberrations consisting of DNA gains within 1p, 1q, 5p, 5q, 7p, 7q, 8q, 11q, 12p, 13q, 16p, 17q, 20q, and losses with 6q, 9p, 10q and 18q. High-level copy gains involved mainly 7p21-p15 and 20q13.3. Dual color fluorescence in situ hybridization (FISH) was performed on a selective locus for validation of array CGH results. Genomic aberrations were compared with different clinicopathological features and a trend of higher number of aberrations in tumors with aggressive phenotypes and current tobacco exposure was identified. According to array CGH data, 23 candidate genes were selected for quantitative PCR (qPCR) analysis. The concordance observed between the genomic and expression changes in most of the genes suggested that they could be candidate cancer-related genes that contributed to the development of lung AD.

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1.	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2.	Paez JG, Jänne PA, Lee JC, et al: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI
3.	Kwak EL, Bang YJ, Camidge DR, et al: Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 363:1693–1703. 2010. View Article : Google Scholar : PubMed/NCBI
4.	Davies JJ, Wilson IM and Lam WL: Array CGH technologies and their applications to cancer genomes. Chromosome Res. 13:237–248. 2005. View Article : Google Scholar : PubMed/NCBI
5.	de Leeuw RJ, Davies JJ, Rosenwald A, et al: Comprehensive whole genome array CGH profiling of mantle cell lymphoma model genomes. Hum Mol Genet. 13:1827–1837. 2004.PubMed/NCBI
6.	Nakao K, Mehta KR, Fridlyand J, et al: High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization. Carcinogenesis. 25:1345–1357. 2004. View Article : Google Scholar : PubMed/NCBI
7.	Wong MP, Fung LF, Wang E, et al: Chromosomal aberrations of primary lung adenocarcinomas in nonsmokers. Cancer. 97:1263–1270. 2003. View Article : Google Scholar : PubMed/NCBI
8.	Zhu H, Lam DC, Han KC, et al: High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines. Cancer Lett. 245:303–314. 2007. View Article : Google Scholar
9.	Lan Q, Hsiung CA, Matsuo K, et al: Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet. 44:1330–1335. 2012. View Article : Google Scholar : PubMed/NCBI
10.	Hsiung CA, Lan Q, Hong YC, et al: The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia. PLoS Genet. 6:e10010512010. View Article : Google Scholar
11.	McKay JD, Hung RJ, Gaborieau V, et al: Lung cancer susceptibility locus at 5p15.33. Nat Genet. 40:1404–1406. 2008. View Article : Google Scholar
12.	Wang Y, Broderick P, Webb E, et al: Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 40:1407–1409. 2008. View Article : Google Scholar
13.	Dong J, Hu Z, Wu C, et al: Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population. Nat Genet. 44:895–899. 2012. View Article : Google Scholar : PubMed/NCBI
14.	Fan B, Dachrut S, Coral H, et al: Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer. PLoS One. 7:e298242012. View Article : Google Scholar : PubMed/NCBI
15.	Holzmann K, Kohlhammer H, Schwaenen C, et al: Genomic DNA-chip hybridization reveals a higher incidence of genomic amplifications in pancreatic cancer than conventional comparative genomic hybridization and leads to the identification of novel candidate genes. Cancer Res. 64:4428–4433. 2004. View Article : Google Scholar
16.	Tonon G, Wong KK, Maulik G, et al: High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci USA. 102:9625–9630. 2005. View Article : Google Scholar : PubMed/NCBI
17.	Kim TM, Yim SH, Lee JS, et al: Genome-wide screening of genomic alterations and their clinicopathologic implications in non-small cell lung cancers. Clin Cancer Res. 11:8235–8242. 2005. View Article : Google Scholar : PubMed/NCBI
18.	Shibata T, Uryu S, Kokubu A, et al: Genetic classification of lung adenocarcinoma based on array-based comparative genomic hybridization analysis: its association with clinicopathologic features. Clin Cancer Res. 11:6177–6185. 2005. View Article : Google Scholar
19.	Rácz A, Brass N, Höfer M, Sybrecht GW, Remberger K and Meese EU: Gene amplification at chromosome 1pter-p33 including the genes PAX7 and ENO1 in squamous cell lung carcinoma. Int J Oncol. 17:67–73. 2000.PubMed/NCBI
20.	Xu X, Padilla MT, Li B, et al: MUC1 in macrophage: contributions to cigarette smoke-induced lung cancer. Cancer Res. 74:460–467. 2014. View Article : Google Scholar : PubMed/NCBI
21.	Yan C, Ding X, Wu L, Yu M, Qu P and Du H: Stat3 downstream gene product chitinase 3-like 1 is a potential biomarker of inflammation-induced lung cancer in multiple mouse lung tumor models and humans. PLoS One. 8:e619842013. View Article : Google Scholar : PubMed/NCBI
22.	Aras G, Kanmaz D, Urer N, Purisa S, Kadakal F, Yentürk E and Tuncay E: Immunohistochemical expression of telomerase in patients with non-small cell lung cancer: prediction of metastasis and prognostic significance. Anticancer Res. 33:2643–2650. 2013.PubMed/NCBI
23.	Lantuéjoul S, Salon C, Soria JC and Brambilla E: Telomerase expression in lung preneoplasia and neoplasia. Int J Cancer. 120:1835–1841. 2007.
24.	Pizzi M, Fassan M, Balistreri M, Galligioni A, Rea F and Rugge M: Anterior gradient 2 overexpression in lung adenocarcinoma. Appl Immunohistochem Mol Morphol. 20:31–36. 2012. View Article : Google Scholar : PubMed/NCBI
25.	Larue L and Delmas V: The WNT/Beta-catenin pathway in melanoma. Front Biosci. 11:733–742. 2006. View Article : Google Scholar : PubMed/NCBI
26.	Zhou XL, Qin XR, Zhang XD and Ye LH: Downregulation of Dickkopf-1 is responsible for high proliferation of breast cancer cells via losing control of Wnt/β-catenin signaling. Acta Pharmacol Sin. 31:202–210. 2010.PubMed/NCBI
27.	Gautschi O, Ratschiller D, Gugger M, Betticher DC and Heighway J: Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung Cancer. 55:1–14. 2007. View Article : Google Scholar : PubMed/NCBI
28.	Gee JM, Eloranta JJ, Ibbitt JC, et al: Overexpression of TFAP2C in invasive breast cancer correlates with a poorer response to anti-hormone therapy and reduced patient survival. J Pathol. 217:32–41. 2009. View Article : Google Scholar : PubMed/NCBI
29.	Lee MH and Surh YJ: eFF1A2 as a putative oncogene. Ann NY Acad Sci. 1171:87–93. 2009. View Article : Google Scholar