Array-based comparative genomic hybridization analysis identified cyclin D1 as a target oncogene at 11q13.3 in nasopharyngeal carcinoma

Angela Bik Yu Hui, Yvonne Yan Yan Or, Hirokuni Takano, Raymond King Yin Tsang, Ka Fai To, Xin Yuen Guan, Jonathan Shun Tong Sham, Katherine Wing Ki Hung, Cleo Nga Yee Lam, Charles Andrew Van Hasselt, Wen Lin Kuo, Joe W. Gray, Dolly P. Huang, Kwok Wai Lo

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86 Scopus citations

Abstract

Nasopharyegeal carcinoma is highly prevalent in Southern China and Southeast Asia. To unveil the molecular basis of this endemic disease, high-resolution comparative genomic hybridization arrays were used for systematic investigation of genomic abnormalities in 26 nasopharyngeal carcinoma samples. A comprehensive picture of genetic lesions associated with tumorigenesis of nasopharyngeal carcinoma was generated. Consistent chromosomal gains were frequently found on 1q, 3q, 8q, 11q, 12p, and 12q. High incidences of nonrandom losses were identified on chromosomes 3p, 9p, 11q, 14q, and 16q. In addition to previously characterized regions, we have identified several novel minimal regions of gains, including 3q27.3-28, 8q21-24, 11q13.1-13.3, and 12q13, which may harbor candidate nasopharyngeal carcinoma-associated oncogenes. In this study, gain of 11q13.1-13.3 was the most frequently detected chromosomal aberration and a 5.3-Mb amplicon was delineated at this region. Within this 11q13 amplicon, concordant amplification and overexpression of cyclin D1 (CCND1) oncogene was found in nasopharyngeal carcinoma cell lines, xenografts, and primary tumors. Knockdown of cyclin D1 by small interfering RNA in nasopharyngeal carcinoma cell lines led to significant decrease of cell proliferation. The findings suggest that cyclin D1 is a target oncogene at 11q13 in nasopharyngeal carcinoma and its activation plays a significant role in nasopharyngeal carcinoma tumorigenesis.

Original languageEnglish (US)
Pages (from-to)8125-8133
Number of pages9
JournalCancer Research
Volume65
Issue number18
DOIs
StatePublished - Sep 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hui, A. B. Y., Or, Y. Y. Y., Takano, H., Tsang, R. K. Y., To, K. F., Guan, X. Y., Sham, J. S. T., Hung, K. W. K., Lam, C. N. Y., Van Hasselt, C. A., Kuo, W. L., Gray, J. W., Huang, D. P., & Lo, K. W. (2005). Array-based comparative genomic hybridization analysis identified cyclin D1 as a target oncogene at 11q13.3 in nasopharyngeal carcinoma. Cancer Research, 65(18), 8125-8133. https://doi.org/10.1158/0008-5472.CAN-05-0648