Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma
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AbstractNasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer commonly occurring in southern China. To decipher the molecular basis of this cancer, we performed high-resolution array CGH analysis on eight tumour lines and 10 primary tumours to identify the genes involved in NPC tumorigenesis. In this study, multiple regions of gain were consistently found at 1q21-q24, 7q11-12, 7q21-22., 11q13, 12p13, 12q13, 19p13 and 19q13. Importantly, a 2.1 Mb region at 12p13.31 was highly amplified in a NPC xenograft, xeno-2117. By FISH mapping, we have further delineated the amplicon to a 1.24 region flanked by RP11-319E16 and RP11-433J6. Copy number gains of this amplicon were confirmed in 21/41 (51%) primary tumours, while three cases (7.3%) showed high copy number amplification. Among the 13 genes within this amplicon, three candidate genes, lymphotoxin beta receptor (LT beta R), tumour necrosis factor receptor superfamily memeber 1A (TNFRSF1R) and FLJI0665, were specifically over-expressed in the NPC xenograft with 12p13.3 amplification. However, only LT beta R was frequently over-expressed in primary tumours. LT beta R is a member of the TNF family of receptors, which can modulate NF-kappa B signalling pathways. Over-expression of LT beta R in nasopharyngeal epithelial cells resulted in an increase of NF-kappa B activity and cell proliferation. In vivo study showed that suppression of LT beta R by siRNA led to growth inhibition in the NPC tumour with 12p13.3 amplification. These findings implied that LT beta R is a potential NPC-associated oncogene within the 12p13.3 amplicon and that its alteration is important in NPC tumorigenesis. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
All Author(s) ListOr YYY, Chung GTY, To KF, Chow C, Choy KW, Tong CYK, Leung AWC, Hui ABY, Tsao SW, Ng HK, Yip TTC, Busson P, Lo KW
Journal nameJournal of Pathology
Year2010
Month1
Day1
Volume Number220
Issue Number1
PublisherJOHN WILEY & SONS LTD
Pages97 - 107
ISSN0022-3417
eISSN1096-9896
LanguagesEnglish-United Kingdom
Keywords12p13.3 amplicon; array CGH; Epstein-Barr virus; LT beta R; nasopharyngeal carcinoma; oncogene
Web of Science Subject CategoriesOncology; ONCOLOGY; Pathology; PATHOLOGY

Last updated on 2020-15-09 at 00:35