EBV Conference 2008 Guangzhou - Baylor College of Medicine

105 (RegID: 1294; 1296; 1297; 1298; 1299)
Grace Chung
Institution: The Chinese University of Hong Kong
e-mail: gracechung@cuhk.edu.hk
A NOVEL 12P13.3 AMPLICON NASOPHARYNGEAL CARCINOMA
Grace Tin-Yun Chung, Yvonne Yan-Yan Or, Ka-Fai To, Siu-Wah Tsao, Timothy TT Yip, Pierre Busson,
Kwok Wai Lo
Posterabstract:
Nasopharyngeal 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 a panel of tumor lines and primary tumors to identify the genes involved in NPC
tumorigenesis. In this study, multiple regions of gain were consistently found at 1q21.2-q21.3, 7q21.3,
11q13.1-13.3, 12p13, 19p13, 19q13. Importantly, a 2.1 Mb region at 12p13.31 was highly amplified in a
NPC xenograft, xeno-2117. By FISH mapping, we 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 tumors while 3 cases (7.3%) showed high copy number amplification. Among the 13 genes
within this amplicon, three candidate genes, LT-beta R (Lymphotoxin-beta receptor), TNFRSF1R (tumor
necrosis factor receptor superfamily, member 1A) and FLJ1066 (PLEKHG6, pleckstrin homology domain
containing, family G (with RhoGef domain) member 6) were specifically overexpressed in xeno-2117
having the 12p13.3 amplification. Of these three candidates, only the LT-beta R was proven to be
frequently overexpressed in primary tumors. As a critical component of NF-kappaB signalling pathway,
LT-beta R was recently reported to be able to transform mouse fibroblast cells. Importantly, aberrant
NF-kappaB signal were found in all EBV-positive NPC tumors and play crucial role in NPC development.
Overexpressing LT-beta R in a normal nasopharyngeal epithelial cell line NP69 resulted in an increase in
NF-kappaB activity. Thus, amplification of LT-beta R may contribute to NPC tumorigenesis by activating
NF-kappaB signal and its downstream genes constitutively. These findings implied that LT-beta R may be
a potential NPC-associated oncogene within 12p13.3 amplicon.
EBV Conference 2008 Guangzhou
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