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Conference Paper: Germline EGFR mutation is uncommon and plays a limited role in predisposition to lung cancer

TitleGermline EGFR mutation is uncommon and plays a limited role in predisposition to lung cancer
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research.
Citation
The 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA., 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, abstract no. LB-131 How to Cite?
AbstractTyrosine kinase inhibitor (TKI) treatment directed against epidermal growth factor receptor (EGFR) has led to dramatic clinical benefits in a group of lung cancer patients - Asian, non-smoking women with adenocarcinoma (AD). Lung cancers associated with this clinical pathological profile often demonstrate somatic EGFR mutations. Our previous study has shown that EGFR mutations are common in our population, involving >50% of all adenocarcinomas and >70% of those from non-smokers, while EGFR double mutations occur in an unusually high proportion of about 13% of untreated lung cancers. Subcloning experiments infer that the double mutations are in cis to each other, occurring on the same allele. These double mutations include a known activating mutation together with an uncommon single amino acid substitution such as T790M. T790M can be occasionally induced as a second mutation in lung cancers previously treated by TKI. It has also been reported as a germline mutation in a family that predisposes to multiple bronchioloalveolar carcinoma formation, in some cases in the presence of an additional somatic activating mutation in cis to T790M. This raises the speculation that in our untreated lung cancers bearing double EGFR mutations, that the uncommon mutant could also be a germline change that predisposes to an activating mutant in cis to itself. We therefore investigated for the possibility of germline EGFR mutations in our population. We screened for 5 mutations (T790M, E709A, E709K, L858M and G873E) found in our lung cancer cases that involved only as one of double mutants but never as the sole mutation in lung adenocarcinomas. 670 alleles from the peripheral mononuclear cells of 335 lung cancer patients were screened. Only one germline mutation, G873E, was found, together with somatic delE746_S752insVP in the tumor. This suggested that germline EGFR mutation is uncommon, and plays a limited role in lung cancer pathogenesis in our population.
Persistent Identifierhttp://hdl.handle.net/10722/104727
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorTam, YSLen_HK
dc.contributor.authorLeung, LHen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorWong, MPen_HK
dc.date.accessioned2010-09-25T22:04:53Z-
dc.date.available2010-09-25T22:04:53Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA., 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, abstract no. LB-131en_HK
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104727-
dc.description.abstractTyrosine kinase inhibitor (TKI) treatment directed against epidermal growth factor receptor (EGFR) has led to dramatic clinical benefits in a group of lung cancer patients - Asian, non-smoking women with adenocarcinoma (AD). Lung cancers associated with this clinical pathological profile often demonstrate somatic EGFR mutations. Our previous study has shown that EGFR mutations are common in our population, involving >50% of all adenocarcinomas and >70% of those from non-smokers, while EGFR double mutations occur in an unusually high proportion of about 13% of untreated lung cancers. Subcloning experiments infer that the double mutations are in cis to each other, occurring on the same allele. These double mutations include a known activating mutation together with an uncommon single amino acid substitution such as T790M. T790M can be occasionally induced as a second mutation in lung cancers previously treated by TKI. It has also been reported as a germline mutation in a family that predisposes to multiple bronchioloalveolar carcinoma formation, in some cases in the presence of an additional somatic activating mutation in cis to T790M. This raises the speculation that in our untreated lung cancers bearing double EGFR mutations, that the uncommon mutant could also be a germline change that predisposes to an activating mutant in cis to itself. We therefore investigated for the possibility of germline EGFR mutations in our population. We screened for 5 mutations (T790M, E709A, E709K, L858M and G873E) found in our lung cancer cases that involved only as one of double mutants but never as the sole mutation in lung adenocarcinomas. 670 alleles from the peripheral mononuclear cells of 335 lung cancer patients were screened. Only one germline mutation, G873E, was found, together with somatic delE746_S752insVP in the tumor. This suggested that germline EGFR mutation is uncommon, and plays a limited role in lung cancer pathogenesis in our population.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Research-
dc.titleGermline EGFR mutation is uncommon and plays a limited role in predisposition to lung canceren_HK
dc.typeConference_Paperen_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.identifier.hkuros137514en_HK
dc.identifier.volume67-
dc.identifier.issue9 suppl.-
dc.publisher.placeUnited States-

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