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Erschienen in: Medical Oncology 4/2011

01.12.2011 | Original Paper

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

Erschienen in: Medical Oncology | Ausgabe 4/2011

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Abstract

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.
Literatur
1.
Zurück zum Zitat Goepfert TM, Brinkley BR. The centrosome-associated aurora/ipl-like kinase family. Curr Top Dev Biol. 2000;49:331–42.PubMedCrossRef Goepfert TM, Brinkley BR. The centrosome-associated aurora/ipl-like kinase family. Curr Top Dev Biol. 2000;49:331–42.PubMedCrossRef
2.
Zurück zum Zitat Kimura M, Okano Y. Aurora kinases and cancer. Gan To Kagaku Ryoho. 2005;32:1–5.PubMed Kimura M, Okano Y. Aurora kinases and cancer. Gan To Kagaku Ryoho. 2005;32:1–5.PubMed
4.
Zurück zum Zitat 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.PubMed 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.PubMed
5.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
6.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
9.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
10.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
11.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
12.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
15.
Zurück zum Zitat Kyrlagkitsis I, Karamanolis DG. Genes and gastric cancer. Hepatogastroenterology. 2004;51:320–7.PubMed Kyrlagkitsis I, Karamanolis DG. Genes and gastric cancer. Hepatogastroenterology. 2004;51:320–7.PubMed
16.
Zurück zum Zitat Wu CW, Chi CW, Lin WC. Gastric cancer. Prognostic and diagnostic advances. Expert Rev Mol Med. 2002;4:1–12.PubMedCrossRef Wu CW, Chi CW, Lin WC. Gastric cancer. Prognostic and diagnostic advances. Expert Rev Mol Med. 2002;4:1–12.PubMedCrossRef
17.
Zurück zum Zitat Kikuchi K, Ueda M, Kitajima M. Molecular biology in gastric cancer. Gan To Kagaku Ryoho. 1999;26:2139–46.PubMed Kikuchi K, Ueda M, Kitajima M. Molecular biology in gastric cancer. Gan To Kagaku Ryoho. 1999;26:2139–46.PubMed
18.
Zurück zum Zitat Dear PH. Copy-number variation. The end of the human genome? Trends Biotechnol. 2009;27:448–54.PubMedCrossRef Dear PH. Copy-number variation. The end of the human genome? Trends Biotechnol. 2009;27:448–54.PubMedCrossRef
19.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
20.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
21.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
22.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
23.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
24.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
25.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
26.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
27.
Zurück zum Zitat Dermitzakis ET, Stranger BE. Genetic variation in human gene expression. Mamm Genome. 2006;17:503–8.PubMedCrossRef Dermitzakis ET, Stranger BE. Genetic variation in human gene expression. Mamm Genome. 2006;17:503–8.PubMedCrossRef
28.
Zurück zum Zitat Reymond A, Henrichsen CN, Harewood L, Merla G. Side effects of genome structural changes. Curr Opin Genet Dev. 2007;17:381–6.PubMedCrossRef Reymond A, Henrichsen CN, Harewood L, Merla G. Side effects of genome structural changes. Curr Opin Genet Dev. 2007;17:381–6.PubMedCrossRef
29.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
30.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
31.
Zurück zum Zitat 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.PubMed 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.PubMed
32.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
33.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
34.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
35.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
36.
Zurück zum Zitat Jeng YM, Peng SY, Lin CY, Hsu HC. Overexpression and amplification of aurora-a in hepatocellular carcinoma. Clin Cancer Res. 2004;10:2065–71.PubMedCrossRef Jeng YM, Peng SY, Lin CY, Hsu HC. Overexpression and amplification of aurora-a in hepatocellular carcinoma. Clin Cancer Res. 2004;10:2065–71.PubMedCrossRef
37.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
38.
Zurück zum Zitat 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. 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.
39.
Zurück zum Zitat 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.PubMed 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.PubMed
40.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
41.
Zurück zum Zitat 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.PubMed 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.PubMed
42.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
Metadaten
Titel
Copy-number increase of AURKA in gastric cancers in a Chinese population: a correlation with tumor progression
Publikationsdatum
01.12.2011
Erschienen in
Medical Oncology / Ausgabe 4/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9602-4

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