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Article: The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS

TitleThe EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS
Authors
KeywordsEGFR
EML4-ALK
Fusion gene
Mucoepidermoid carcinoma
Nonsmall cell lung cancer
Nonsmoker
Issue Date2009
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2009, v. 115 n. 8, p. 1723-1733 How to Cite?
AbstractBackground: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4- ALK) fusion gene resulting from the chromosome inversion inv(2)(p21;p23) recently was identified in non- small cell lung cancer (NSCLC). The authors of this study investigated the frequency, genetic and clinicopathologic profiles of EML4-ALK in Chinese patients with NSCLC. Methods: EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing. EML4-ALK protein expression was studied by immunohistochemistry. Results: Thirteen tumors (4.9%) had EML4-ALK comprising 4 fusion transcript variants with fusion of the variable segments from 5' EML4 to 3' ALK and with preservation of the ALK kinase domain. The most common variant consisted of 8 tumors with variant 3 that involved EML4 exon 6. The others included 2 tumors with variant 1 (exon 13), 2 tumors with variant 2 (exon 20), and 1 tumor with the novel variant 5 (exon 18). There were 11 ADs and 2 unusual carcinomas with mixed squamous and glandular components. Immunohistochemistry demonstrated diffuse ALK fusion proteins in the tumor cell cytoplasm. EML4-ALK was associated with nonsmokers (P = .009). Tumors with the fusion gene had the wild-type epidermal growth factor receptor (EGFR)(P = .001) and v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) genes. Patients who had EML4-ALK-positive AD had a younger median age (P = .018) compared with patients who did not have the fusion gene. Conclusions: The EML4-ALK fusion gene was present in various histologic types of NSCLC. It occurred in mutual exclusion to EGFR and KRAS mutations and was associated with nonsmokers. The authors concluded that EML4-ALK may be useful for predicting the potential response to ALK inhibitors as a therapeutic option for patients with lung cancer. © 2009 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/60569
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
Funding AgencyGrant Number
General Research FundHKU/778708
Research Grants Council (Hong Kong Government)
University of Hong Kong10207989
Funding Information:

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.authorSo, KKTen_HK
dc.contributor.authorTam, IYSen_HK
dc.contributor.authorSihoe, ADLen_HK
dc.contributor.authorCheng, LCen_HK
dc.contributor.authorHo, KKen_HK
dc.contributor.authorAu, JSKen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorWong, MPen_HK
dc.date.accessioned2010-05-31T04:13:52Z-
dc.date.available2010-05-31T04:13:52Z-
dc.date.issued2009en_HK
dc.identifier.citationCancer, 2009, v. 115 n. 8, p. 1723-1733en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/60569-
dc.description.abstractBackground: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4- ALK) fusion gene resulting from the chromosome inversion inv(2)(p21;p23) recently was identified in non- small cell lung cancer (NSCLC). The authors of this study investigated the frequency, genetic and clinicopathologic profiles of EML4-ALK in Chinese patients with NSCLC. Methods: EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing. EML4-ALK protein expression was studied by immunohistochemistry. Results: Thirteen tumors (4.9%) had EML4-ALK comprising 4 fusion transcript variants with fusion of the variable segments from 5' EML4 to 3' ALK and with preservation of the ALK kinase domain. The most common variant consisted of 8 tumors with variant 3 that involved EML4 exon 6. The others included 2 tumors with variant 1 (exon 13), 2 tumors with variant 2 (exon 20), and 1 tumor with the novel variant 5 (exon 18). There were 11 ADs and 2 unusual carcinomas with mixed squamous and glandular components. Immunohistochemistry demonstrated diffuse ALK fusion proteins in the tumor cell cytoplasm. EML4-ALK was associated with nonsmokers (P = .009). Tumors with the fusion gene had the wild-type epidermal growth factor receptor (EGFR)(P = .001) and v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) genes. Patients who had EML4-ALK-positive AD had a younger median age (P = .018) compared with patients who did not have the fusion gene. Conclusions: The EML4-ALK fusion gene was present in various histologic types of NSCLC. It occurred in mutual exclusion to EGFR and KRAS mutations and was associated with nonsmokers. The authors concluded that EML4-ALK may be useful for predicting the potential response to ALK inhibitors as a therapeutic option for patients with lung cancer. © 2009 American Cancer Society.en_HK
dc.languageengen_HK
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.en_HK
dc.subjectEGFRen_HK
dc.subjectEML4-ALKen_HK
dc.subjectFusion geneen_HK
dc.subjectMucoepidermoid carcinomaen_HK
dc.subjectNonsmall cell lung canceren_HK
dc.subjectNonsmokeren_HK
dc.subject.meshAgeden_HK
dc.subject.meshCarcinoma, Non-Small-Cell Lung - genetics - pathologyen_HK
dc.subject.meshChromosome Breakageen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenes, rasen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLung Neoplasms - genetics - pathologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMutationen_HK
dc.subject.meshOncogene Proteins, Fusion - geneticsen_HK
dc.subject.meshReceptor, Epidermal Growth Factor - geneticsen_HK
dc.subject.meshSmokingen_HK
dc.titleThe EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRASen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-543X&volume=115&spage=1723&epage=1733&date=2009&atitle=The+Eml4-alk+Fusion+Gene+Is+Involved+In+Various+Histologic+Types+Of+Lung+Cancers+From+Nonsmokers+With+Wild-type+Egfr+And+Krasen_HK
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.24181en_HK
dc.identifier.pmid19170230-
dc.identifier.scopuseid_2-s2.0-65249095599en_HK
dc.identifier.hkuros155784en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65249095599&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume115en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1723en_HK
dc.identifier.epage1733en_HK
dc.identifier.eissn1097-0142-
dc.identifier.isiWOS:000264918700017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f100013354000-
dc.identifier.scopusauthoridWong, DWS=26532106600en_HK
dc.identifier.scopusauthoridLeung, ELH=26531254500en_HK
dc.identifier.scopusauthoridSo, KKT=12040682800en_HK
dc.identifier.scopusauthoridTam, IYS=8244035800en_HK
dc.identifier.scopusauthoridSihoe, ADL=6603611976en_HK
dc.identifier.scopusauthoridCheng, LC=9533935800en_HK
dc.identifier.scopusauthoridHo, KK=9536814400en_HK
dc.identifier.scopusauthoridAu, JSK=7101921203en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridWong, MP=7403907887en_HK

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