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Article: Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma

TitleIdentification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma
Authors
Issue Date2010
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
Citation
Journal Of Pathology, 2010, v. 220 n. 1, p. 97-107 How to Cite?
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 (LTβR), tumour necrosis factor receptor superfamily memeber 1A (TNFRSF1R) and FLJ10665, were specifically over-expressed in the NPC xenograft with 12p13.3 amplification. However, only LTβR was frequently over-expressed in primary tumours. LTβR is a member of the TNF family of receptors, which can modulate NF-κB signalling pathways. Over-expression of LTβR in nasopharyngeal epithelial cells resulted in an increase of NF-κB activity and cell proliferation. In vivo study showed that suppression of LTβR by siRNA led to growth inhibition in the NPC tumour with 12p13.3 amplification. These findings implied that LTβR is a potential NPC-associated oncogene within the 12p13.3 amplicon and that its alteration is important in NPC tumorigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/149726
ISSN
2015 Impact Factor: 7.381
2015 SCImago Journal Rankings: 4.176
ISI Accession Number ID
Funding AgencyGrant Number
Michael and Betty Kadoorie Cancer Genetics Research
Li Ka Shing Institute of Health Science
Hong Kong Research Grant Council470708
Funding Information:

This work was supported by the Michael and Betty Kadoorie Cancer Genetics Research Program II (MBKCGRPII), Li Ka Shing Institute of Health Science and Hong Kong Research Grant Council (Grant No. 470708).

References

 

DC FieldValueLanguage
dc.contributor.authorOr, YYYen_US
dc.contributor.authorChung, GTYen_US
dc.contributor.authorTo, KFen_US
dc.contributor.authorChow, Cen_US
dc.contributor.authorChoy, KWen_US
dc.contributor.authorTong, CYKen_US
dc.contributor.authorLeung, AWCen_US
dc.contributor.authorHui, ABYen_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorNg, HKen_US
dc.contributor.authorYip, TTCen_US
dc.contributor.authorBusson, Pen_US
dc.contributor.authorLo, KWen_US
dc.date.accessioned2012-06-26T05:57:41Z-
dc.date.available2012-06-26T05:57:41Z-
dc.date.issued2010en_US
dc.identifier.citationJournal Of Pathology, 2010, v. 220 n. 1, p. 97-107en_US
dc.identifier.issn0022-3417en_US
dc.identifier.urihttp://hdl.handle.net/10722/149726-
dc.description.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 (LTβR), tumour necrosis factor receptor superfamily memeber 1A (TNFRSF1R) and FLJ10665, were specifically over-expressed in the NPC xenograft with 12p13.3 amplification. However, only LTβR was frequently over-expressed in primary tumours. LTβR is a member of the TNF family of receptors, which can modulate NF-κB signalling pathways. Over-expression of LTβR in nasopharyngeal epithelial cells resulted in an increase of NF-κB activity and cell proliferation. In vivo study showed that suppression of LTβR by siRNA led to growth inhibition in the NPC tumour with 12p13.3 amplification. These findings implied that LTβR is a potential NPC-associated oncogene within the 12p13.3 amplicon and that its alteration is important in NPC tumorigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130en_US
dc.relation.ispartofJournal of Pathologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshChromosomes, Human, Pair 12 - Geneticsen_US
dc.subject.meshComparative Genomic Hybridizationen_US
dc.subject.meshGene Amplificationen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Knockdown Techniquesen_US
dc.subject.meshHumansen_US
dc.subject.meshIn Situ Hybridization, Fluorescenceen_US
dc.subject.meshLymphotoxin Beta Receptor - Biosynthesis - Geneticsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshNasopharyngeal Neoplasms - Genetics - Metabolism - Pathologyen_US
dc.subject.meshNeoplasm Proteins - Biosynthesis - Geneticsen_US
dc.subject.meshNeoplasm Transplantationen_US
dc.subject.meshOncogenesen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction - Methodsen_US
dc.subject.meshSignal Transduction - Genetics - Physiologyen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTransplantation, Heterologousen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.titleIdentification of a novel 12p13.3 amplicon in nasopharyngeal carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_US
dc.identifier.authorityTsao, SW=rp00399en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/path.2609en_US
dc.identifier.pmid19718711-
dc.identifier.scopuseid_2-s2.0-73649128345en_US
dc.identifier.hkuros182746-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73649128345&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume220en_US
dc.identifier.issue1en_US
dc.identifier.spage97en_US
dc.identifier.epage107en_US
dc.identifier.isiWOS:000273186100011-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridOr, YYY=8940434900en_US
dc.identifier.scopusauthoridChung, GTY=9246670000en_US
dc.identifier.scopusauthoridTo, KF=7101911940en_US
dc.identifier.scopusauthoridChow, C=35739799700en_US
dc.identifier.scopusauthoridChoy, KW=7005477052en_US
dc.identifier.scopusauthoridTong, CYK=7202716275en_US
dc.identifier.scopusauthoridLeung, AWC=7403012691en_US
dc.identifier.scopusauthoridHui, ABY=7102453683en_US
dc.identifier.scopusauthoridTsao, SW=7102813116en_US
dc.identifier.scopusauthoridNg, HK=7401619354en_US
dc.identifier.scopusauthoridYip, TTC=19236471100en_US
dc.identifier.scopusauthoridBusson, P=7005088091en_US
dc.identifier.scopusauthoridLo, KW=34872774800en_US

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