Medical Oncology

, Volume 28, Issue 4, pp 1017–1022 | Cite as

Copy-number increase of AURKA in gastric cancers in a Chinese population: a correlation with tumor progression

  • Zhengyu Fang
  • Yi Xiong
  • Jiana Li
  • Li Liu
  • Manhui Li
  • Chao Zhang
  • Wei Zhang
  • Jun WanEmail author
Original Paper


The centrosome-associated kinase aurora A (AURKA) has been shown to be involved in genetic instability and to be over-expressed in several human carcinomas including gastric cancers (GCs). The chromosome locus of AURKA, 20q13, is frequently amplified in GCs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of gastric carcinomas and adjacent normal epithelium (n = 141) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA expression of AURKA in GCs. Our results showed copy-number gains of AUKRA were detected in a relative high percentage of GC samples (30.5%, 43 out of 141). There was a positive correlation between copy-number increase of AURKA and tumor progression. And copy-number gains of AURKA also showed a positive correlation with mRNA over-expression in GCs. However, expression level of AURKA mRNA was also enhanced in the group of GC samples with unaltered copy numbers. These findings indicated that sporadic gastric cancers exhibit different mechanisms of AURKA regulation and that this may impact the efficacy of aurora-targeted therapies.


Gastric cancer AURKA Copy-number variation Gene expression 


  1. 1.
    Goepfert TM, Brinkley BR. The centrosome-associated aurora/ipl-like kinase family. Curr Top Dev Biol. 2000;49:331–42.PubMedCrossRefGoogle Scholar
  2. 2.
    Kimura M, Okano Y. Aurora kinases and cancer. Gan To Kagaku Ryoho. 2005;32:1–5.PubMedGoogle Scholar
  3. 3.
    Ikezoe T. Aurora kinases as an anti-cancer target. Cancer Lett. 2008;262(1):1–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Kamada K, Yamada Y, Hirao T, Fujimoto H, Takahama Y, et al. Amplification/overexpression of aurora-a in human gastric carcinoma. Potential role in differentiated type gastric carcinogenesis. Oncol Rep. 2004;12:593–9.PubMedGoogle Scholar
  5. 5.
    Dar AA, Zaika A, Piazuelo MB, Correa P, Koyama T, et al. Frequent overexpression of aurora kinase a in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer. 2008;112:1688–98.PubMedCrossRefGoogle Scholar
  6. 6.
    Park HS, Park WS, Bondaruk J, Tanaka N, Katayama H, et al. Quantitation of aurora kinase a gene copy number in urine sediments and bladder cancer detection. J Natl Cancer Inst. 2008;100:1401–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Andrews J, Kennette W, Pilon J, Hodgson A, Tuck AB, et al. Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number. PLoS One. 2010;5:e8665.PubMedCrossRefGoogle Scholar
  8. 8.
    Diskin SJ, Hou C, Glessner JT, Attiyeh EF, Laudenslager M, et al. Copy number variation at 1q21.1 associated with neuroblastoma. Nature. 2009;459:987–91.PubMedCrossRefGoogle Scholar
  9. 9.
    Liu W, Sun J, Li G, Zhu Y, Zhang S, et al. Association of a germ-line copy number variation at 2p24.3 and risk for aggressive prostate cancer. Cancer Res. 2009;69:2176–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Buffart TE, van Grieken NC, Tijssen M, Coffa J, Ylstra B, et al. High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers. Virchows Arch. 2009;455:213–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Sakakura C, Mori T, Sakabe T, Ariyama Y, Shinomiya T, et al. Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization. Genes Chromosom Cancer. 1999;24:299–305.PubMedCrossRefGoogle Scholar
  12. 12.
    Vauhkonen H, Vauhkonen M, Sajantila A, Sipponen P, Knuutila S. DNA copy number aberrations in intestinal-type gastric cancer revealed by array-based comparative genomic hybridization. Cancer Genet Cytogenet. 2006;167:150–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Lam AK, Ong K, Ho YH. Aurora kinase expression in colorectal adenocarcinoma. Correlations with clinicopathological features, p16 expression, and telomerase activity. Hum Pathol. 2008;39:599–604.PubMedCrossRefGoogle Scholar
  14. 14.
    Lassmann S, Danciu M, Muller M, Weis R, Makowiec F, et al. Aurora a is differentially expressed and regulated in chromosomal and microsatellite instable sporadic colorectal cancers. Mod Pathol. 2009;22:1385–97.PubMedCrossRefGoogle Scholar
  15. 15.
    Kyrlagkitsis I, Karamanolis DG. Genes and gastric cancer. Hepatogastroenterology. 2004;51:320–7.PubMedGoogle Scholar
  16. 16.
    Wu CW, Chi CW, Lin WC. Gastric cancer. Prognostic and diagnostic advances. Expert Rev Mol Med. 2002;4:1–12.PubMedCrossRefGoogle Scholar
  17. 17.
    Kikuchi K, Ueda M, Kitajima M. Molecular biology in gastric cancer. Gan To Kagaku Ryoho. 1999;26:2139–46.PubMedGoogle Scholar
  18. 18.
    Dear PH. Copy-number variation. The end of the human genome? Trends Biotechnol. 2009;27:448–54.PubMedCrossRefGoogle Scholar
  19. 19.
    Shlien A, Tabori U, Marshall CR, Pienkowska M, Feuk L, et al. Excessive genomic DNA copy number variation in the li-fraumeni cancer predisposition syndrome. Proc Natl Acad Sci USA. 2008;105:11264–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Grubor V, Krasnitz A, Troge JE, Meth JL, Lakshmi B, et al. Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (roma). Blood. 2009;113:1294–303.PubMedCrossRefGoogle Scholar
  21. 21.
    Gunnarsson R, Staaf J, Jansson M, Ottesen AM, Goransson H, et al. Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia–a comparative study of four differently designed, high resolution microarray platforms. Genes Chromosom Cancer. 2008;47:697–711.PubMedCrossRefGoogle Scholar
  22. 22.
    Schafer M, Schwender H, Merk S, Haferlach C, Ickstadt K, et al. Integrated analysis of copy number alterations and gene expression. A bivariate assessment of equally directed abnormalities. Bioinformatics. 2009;25:3228–35.PubMedCrossRefGoogle Scholar
  23. 23.
    Strefford JC, van Delft FW, Robinson HM, Worley H, Yiannikouris O, et al. Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Proc Natl Acad Sci USA. 2006;103:8167–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Sulong S, Moorman AV, Irving JA, Strefford JC, Konn ZJ, et al. A comprehensive analysis of the cdkn2a gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups. Blood. 2009;113:100–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Vauhkonen H, Vauhkonen M, Sipponen P, Knuutila S. Oligonucleotide array comparative genomic hybridization refines the structure of 8p23.1, 17q12 and 20q13.2 amplifications in gastric carcinomas. Cytogenet Genome Res. 2007;119:39–45.PubMedCrossRefGoogle Scholar
  26. 26.
    Aust DE, Muders M, Kohler A, Schmidt M, Diebold J, et al. Prognostic relevance of 20q13 gains in sporadic colorectal cancers. A fish analysis. Scand J Gastroenterol. 2004;39:766–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Dermitzakis ET, Stranger BE. Genetic variation in human gene expression. Mamm Genome. 2006;17:503–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Reymond A, Henrichsen CN, Harewood L, Merla G. Side effects of genome structural changes. Curr Opin Genet Dev. 2007;17:381–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Guryev V, Saar K, Adamovic T, Verheul M, van Heesch SA, et al. Distribution and functional impact of DNA copy number variation in the rat. Nat Genet. 2008;40:538–45.PubMedCrossRefGoogle Scholar
  30. 30.
    Henrichsen CN, Vinckenbosch N, Zollner S, Chaignat E, Pradervand S, et al. Segmental copy number variation shapes tissue transcriptomes. Nat Genet. 2009;41:424–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Fujita Y, Sakakura C, Shimomura K, Nakanishi M, Yasuoka R, et al. Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization. Hepatogastroenterology. 2003;50:1857–63.PubMedGoogle Scholar
  32. 32.
    Agnese V, Cabibi D, Calcara D, Terrasi M, Pantuso G, et al. Aurora-a overexpression as an early marker of reflux-related columnar mucosa and barrett’s oesophagus. Ann Oncol. 2007;18(Suppl 6):vi110–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Tong T, Zhong Y, Kong J, Dong L, Song Y, et al. Overexpression of aurora-a contributes to malignant development of human esophageal squamous cell carcinoma. Clin Cancer Res. 2004;10:7304–10.PubMedCrossRefGoogle Scholar
  34. 34.
    Tanaka E, Hashimoto Y, Ito T, Okumura T, Kan T, et al. The clinical significance of aurora-a/stk15/btak expression in human esophageal squamous cell carcinoma. Clin Cancer Res. 2005;11:1827–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Yamashita K, Igarashi H, Kitayama Y, Ozawa T, Kiyose S, et al. Chromosomal numerical abnormality profiles of gastrointestinal stromal tumors. Jpn J Clin Oncol. 2006;36:85–92.PubMedCrossRefGoogle Scholar
  36. 36.
    Jeng YM, Peng SY, Lin CY, Hsu HC. Overexpression and amplification of aurora-a in hepatocellular carcinoma. Clin Cancer Res. 2004;10:2065–71.PubMedCrossRefGoogle Scholar
  37. 37.
    Rojanala S, Han H, Munoz RM, Browne W, Nagle R, et al. The mitotic serine threonine kinase, aurora-2, is a potential target for drug development in human pancreatic cancer. Mol Cancer Ther. 2004;3:451–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Zhu J, Abbruzzese JL, Izzo J, Hittelman WN, Li D. Aurka amplification, chromosome instability, and centrosome abnormality in human pancreatic carcinoma cells. Cancer Genet Cytogenet. 2003;2005:159.10–7.Google Scholar
  39. 39.
    Li D, Zhu J, Firozi PF, Abbruzzese JL, Evans DB, et al. Overexpression of oncogenic stk15/btak/aurora a kinase in human pancreatic cancer. Clin Cancer Res. 2003;9:991–7.PubMedGoogle Scholar
  40. 40.
    Nishida N, Nagasaka T, Kashiwagi K, Boland CR, Goel A. High copy amplification of the aurora-a gene is associated with chromosomal instability phenotype in human colorectal cancers. Cancer Biol Ther. 2007;6:525–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Baba Y, Nosho K, Shima K, Irahara N, Kure S, et al. Aurora-a expression is independently associated with chromosomal instability in colorectal cancer. Neoplasia. 2009;11:418–25.PubMedGoogle Scholar
  42. 42.
    Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nakanishi M, et al. Tumour-amplified kinase btak is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer. 2001;84:824–31.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Zhengyu Fang
    • 1
  • Yi Xiong
    • 1
  • Jiana Li
    • 1
  • Li Liu
    • 1
  • Manhui Li
    • 1
  • Chao Zhang
    • 1
  • Wei Zhang
    • 2
  • Jun Wan
    • 1
    Email author
  1. 1.Biomedical Research InstituteShenzhen-PKU-HKUST Medical CenterShenzhenPeople’s Republic of China
  2. 2.JNU-HKUST Joint LabJi-Nan UniversityGuangdongPeople’s Republic of China

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