Array-based comparative genomic hybridization analysis identified cyclin D1 as a target oncogene at 11q13.3 in nasopharyngeal carcinoma.
Nasopharyngeal 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.
Hui
Angela Bik-Yu
AB
Departments of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
Or
Yvonne Yan-Yan
YY
Takano
Hirokuni
H
Tsang
Raymond King-Yin
RK
To
Ka-Fai
KF
Guan
Xin-Yuen
XY
Sham
Jonathan Shun-Tong
JS
Hung
Katherine Wing-Ki
KW
Lam
Cleo Nga-Yee
CN
van Hasselt
Charles Andrew
CA
Kuo
Wen-Lin
WL
Gray
Joe W
JW
Huang
Dolly P
DP
Lo
Kwok-Wai
KW
D000818:Animals; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005784:Gene Amplification; D019940:Genes, bcl-1 / Q000235:genetics*; D006801:Humans; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous
D034741:RNA, Small Interfering