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Article: A novel KIF5B-ALK variant in nonsmall cell lung cancer

TitleA novel KIF5B-ALK variant in nonsmall cell lung cancer
Authors
KeywordsEML4-ALK
fusion gene
KIF5B-ALK
nonsmall cell lung cancer
oncogenesis
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2011, v. 117 n. 12, p. 2709-2718 How to Cite?
AbstractBACKGROUND: The anaplastic lymphoma kinase (ALK) gene is involved frequently in chromosomal translocations, resulting in fusion genes with different partners found in various lymphoproliferative conditions. It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene conferred oncogenic properties. The objective of the current study was to identify other possible ALK fusion genes in NSCLC. METHODS: Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. The authors used 5′ rapid amplification of complementary DNA ends to screen for potential, novel 5′ fusion partners of ALK other than EML4-ALK. Reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization analyses were used to confirm the identity of 5′ fusion partners. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4-ALK was performed to assess downstream signaling and functional effects. RESULTS: The authors identified a novel gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot analysis of clinical tumor tissues revealed the expression of a protein whose size correlated with that of the predicted KIF5B-ALK. Overexpression of KIF5B-ALK in mammalian cells led to the activation of signal transducer and activator of transcription 3 and protein kinase B and to enhanced cell proliferation, migration, and invasion. CONCLUSIONS: The discovery of the novel KIF5B-ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis. Copyright © 2011 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/133346
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council (Hong Kong Government)HKU/778708
Committee on Research and Conference Grants, University of Hong Kong10207989
Funding Information:

This work was supported by a grant from the General Research Fund (HKU/778708) awarded by the Research Grants Council (Hong Kong Government) and by a grant from the Small Project Fund (10207989) awarded by the Committee on Research and Conference Grants, University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorWong, DWSen_HK
dc.contributor.authorLeung, ELHen_HK
dc.contributor.authorWong, SKMen_HK
dc.contributor.authorTin, VPCen_HK
dc.contributor.authorSihoe, ADLen_HK
dc.contributor.authorCheng, LCen_HK
dc.contributor.authorAu, JSKen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorWong, MPen_HK
dc.date.accessioned2011-05-11T08:32:42Z-
dc.date.available2011-05-11T08:32:42Z-
dc.date.issued2011en_HK
dc.identifier.citationCancer, 2011, v. 117 n. 12, p. 2709-2718en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/133346-
dc.description.abstractBACKGROUND: The anaplastic lymphoma kinase (ALK) gene is involved frequently in chromosomal translocations, resulting in fusion genes with different partners found in various lymphoproliferative conditions. It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene conferred oncogenic properties. The objective of the current study was to identify other possible ALK fusion genes in NSCLC. METHODS: Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. The authors used 5′ rapid amplification of complementary DNA ends to screen for potential, novel 5′ fusion partners of ALK other than EML4-ALK. Reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization analyses were used to confirm the identity of 5′ fusion partners. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4-ALK was performed to assess downstream signaling and functional effects. RESULTS: The authors identified a novel gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot analysis of clinical tumor tissues revealed the expression of a protein whose size correlated with that of the predicted KIF5B-ALK. Overexpression of KIF5B-ALK in mammalian cells led to the activation of signal transducer and activator of transcription 3 and protein kinase B and to enhanced cell proliferation, migration, and invasion. CONCLUSIONS: The discovery of the novel KIF5B-ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis. Copyright © 2011 American Cancer Society.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.rightsCancer. Copyright © John Wiley & Sons, Inc.-
dc.subjectEML4-ALKen_HK
dc.subjectfusion geneen_HK
dc.subjectKIF5B-ALKen_HK
dc.subjectnonsmall cell lung canceren_HK
dc.subjectoncogenesisen_HK
dc.titleA novel KIF5B-ALK variant in nonsmall cell lung canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-543X&volume=117&issue=12&spage=2709&epage=2718&date=2011&atitle=A+novel+KIF5B-ALK+variant+in+nonsmall+cell+lung+cancer-
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.emailWong, MP: mwpik@hkucc.hku.hken_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.authorityWong, MP=rp00348en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/cncr.25843en_HK
dc.identifier.pmid21656749-
dc.identifier.scopuseid_2-s2.0-79955973559en_HK
dc.identifier.hkuros184975en_US
dc.identifier.hkuros247047-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955973559&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume117en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2709en_HK
dc.identifier.epage2718en_HK
dc.identifier.isiWOS:000291450100019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f100013353980-
dc.identifier.scopusauthoridWong, DWS=26532106600en_HK
dc.identifier.scopusauthoridLeung, ELH=26531254500en_HK
dc.identifier.scopusauthoridWong, SKM=48661627100en_HK
dc.identifier.scopusauthoridTin, VPC=6603199735en_HK
dc.identifier.scopusauthoridSihoe, ADL=6603611976en_HK
dc.identifier.scopusauthoridCheng, LC=9533935800en_HK
dc.identifier.scopusauthoridAu, JSK=7101921203en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridWong, MP=7403907887en_HK

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