title: Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma.
abstract: 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 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 (LTbetaR), tumour necrosis factor receptor superfamily memeber 1A (TNFRSF1R) and FLJ10665, were specifically over-expressed in the NPC xenograft with 12p13.3 amplification. However, only LTbetaR was frequently over-expressed in primary tumours. LTbetaR is a member of the TNF family of receptors, which can modulate NF-kappaB signalling pathways. Over-expression of LTbetaR in nasopharyngeal epithelial cells resulted in an increase of NF-kappaB activity and cell proliferation. In vivo study showed that suppression of LTbetaR by siRNA led to growth inhibition in the NPC tumour with 12p13.3 amplification. These findings implied that LTbetaR is a potential NPC-associated oncogene within the 12p13.3 amplicon and that its alteration is important in NPC tumorigenesis.
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
authors.forename: Yvonne Y-Y
authors.initials: YY
authors.lastname: Or
authors.forename: Grace T-Y
authors.initials: GT
authors.lastname: Chung
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.forename: Chit
authors.initials: C
authors.lastname: Chow
authors.forename: Kwong-Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Carol Y-K
authors.initials: CY
authors.lastname: Tong
authors.forename: Alice W-C
authors.initials: AW
authors.lastname: Leung
authors.forename: Angela B-Y
authors.initials: AB
authors.lastname: Hui
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Timothy T-C
authors.initials: TT
authors.lastname: Yip
authors.forename: Pierre
authors.initials: P
authors.lastname: Busson
authors.forename: Kwok-Wai
authors.initials: KW
authors.lastname: Lo
mesh_terms: D000818:Animals; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053259:Lymphotoxin beta Receptor / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D009857:Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D009363:Neoplasm Proteins