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Conference Paper: EGFR mutations are prevalent and independent from k-RAS mutations in lung adenocarcinomas from non-smokers

TitleEGFR mutations are prevalent and independent from k-RAS mutations in lung adenocarcinomas from non-smokers
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research
Citation
AACR 96th Annual Meeting, Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 392-393 Abstract no. 5365 p. 1666 How to Cite?
AbstractLung cancer is common in Hong Kong with an unusually high incidence in female non-smokers (NS). Lung cancers in NS are likely to involve different carcinogenic processes from those in smokers, but the molecular targets are unclear. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a crucial role in cell proliferation, survival and differentiation. It has been observed that non-small cell lung cancer (NSCLC) patients showing improved clinical response to tyrosine kinase inhibitor (TKI) treatment harbour somatic mutations in EGFR tyrosine kinase domain. Activating point mutations in the RAS oncogene has been recognized in adenocarcinomas of different organs including the lung. In order to find out the prevalence and patterns of EGFR and RAS mutations, as well as their relation with clinicopathological profiles of primary NSCLC in Hong Kong, 228 surgically resected primary lung cancers were analyzed. The tumors included 205 adenocarcinomas (AD), 14 squamous cell carcinomas (SCC) and 9 lymphoepithelioma-like carcinomas (LELC) from 97 men (55 current smokers (SM), 17 NS, 24 ex-smokers (EX) and 1 passive smokers (PS)), and 131 women (7 SM, 92 NS, 13 EX and 19 PS) were studied. PCR amplified products spanning the EGFR mutation hot spots (exons 18-21) were sequenced. An overall mutation rate of 49.1% (112/228) was observed, including 52 in-frame deletions, 5 in-frame insertions and 55 amino acid substitutions. Statistically significant associations were found between EGFR mutations and a) NS (79/109) compared with patients with any level of current or previous tobacco exposure (33/119 SM, PS, EX) or with SM only (12/62), P<0.0001 for both, b) female (83/131) compared to male (29/97), P<0.0001 and c) AD (112/205) compared to non-AD (0/23), P<0.0001. No association was found with patients’ age and pathological tumor stage. The findings suggest that EGFR mutation mediates important non-tobacco induced carcinogenic pathways in AD from NS, in contrast to SCC that are prevalent in smokers or the Epstein Barr virus-related LELC. The frequency of K-RAS codon 12 mutations was analyzed by dot-blot and sequencing which demonstrated 18/228 (7.9%) mutations. The mutations were significantly associated with history of any tobacco exposure (15/119, P=0.006) or SM only (10/62, P=0.002). Furthermore, all the K-RAS mutants were found in tumours with wild type EGFR (P<0.0001). In conclusion, EGFR mutations are prevalent and independent from K-RAS mutations in the carcinogenic process in NS with AD. EGFR mutation status of these patients is useful for predicting potential response to TKI therapy. (Supported by HKSAR RGC grants 7310/01M, 7486/03M, 7468/04M)
Persistent Identifierhttp://hdl.handle.net/10722/104665
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorTam, IYSen_HK
dc.contributor.authorWong, MPen_HK
dc.contributor.authorSuen, WSen_HK
dc.contributor.authorWang, Een_HK
dc.contributor.authorLam, WKen_HK
dc.contributor.authorChiu, SWen_HK
dc.contributor.authorGazdar, Aen_HK
dc.contributor.authorMinna, JDen_HK
dc.contributor.authorChung, LPen_HK
dc.date.accessioned2010-09-25T22:02:23Z-
dc.date.available2010-09-25T22:02:23Z-
dc.date.issued2005en_HK
dc.identifier.citationAACR 96th Annual Meeting, Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 392-393 Abstract no. 5365 p. 1666en_HK
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104665-
dc.description.abstractLung cancer is common in Hong Kong with an unusually high incidence in female non-smokers (NS). Lung cancers in NS are likely to involve different carcinogenic processes from those in smokers, but the molecular targets are unclear. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a crucial role in cell proliferation, survival and differentiation. It has been observed that non-small cell lung cancer (NSCLC) patients showing improved clinical response to tyrosine kinase inhibitor (TKI) treatment harbour somatic mutations in EGFR tyrosine kinase domain. Activating point mutations in the RAS oncogene has been recognized in adenocarcinomas of different organs including the lung. In order to find out the prevalence and patterns of EGFR and RAS mutations, as well as their relation with clinicopathological profiles of primary NSCLC in Hong Kong, 228 surgically resected primary lung cancers were analyzed. The tumors included 205 adenocarcinomas (AD), 14 squamous cell carcinomas (SCC) and 9 lymphoepithelioma-like carcinomas (LELC) from 97 men (55 current smokers (SM), 17 NS, 24 ex-smokers (EX) and 1 passive smokers (PS)), and 131 women (7 SM, 92 NS, 13 EX and 19 PS) were studied. PCR amplified products spanning the EGFR mutation hot spots (exons 18-21) were sequenced. An overall mutation rate of 49.1% (112/228) was observed, including 52 in-frame deletions, 5 in-frame insertions and 55 amino acid substitutions. Statistically significant associations were found between EGFR mutations and a) NS (79/109) compared with patients with any level of current or previous tobacco exposure (33/119 SM, PS, EX) or with SM only (12/62), P<0.0001 for both, b) female (83/131) compared to male (29/97), P<0.0001 and c) AD (112/205) compared to non-AD (0/23), P<0.0001. No association was found with patients’ age and pathological tumor stage. The findings suggest that EGFR mutation mediates important non-tobacco induced carcinogenic pathways in AD from NS, in contrast to SCC that are prevalent in smokers or the Epstein Barr virus-related LELC. The frequency of K-RAS codon 12 mutations was analyzed by dot-blot and sequencing which demonstrated 18/228 (7.9%) mutations. The mutations were significantly associated with history of any tobacco exposure (15/119, P=0.006) or SM only (10/62, P=0.002). Furthermore, all the K-RAS mutants were found in tumours with wild type EGFR (P<0.0001). In conclusion, EGFR mutations are prevalent and independent from K-RAS mutations in the carcinogenic process in NS with AD. EGFR mutation status of these patients is useful for predicting potential response to TKI therapy. (Supported by HKSAR RGC grants 7310/01M, 7486/03M, 7468/04M)-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleEGFR mutations are prevalent and independent from k-RAS mutations in lung adenocarcinomas from non-smokersen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailTam, IYS: h9718676@graduate.hku.hken_HK
dc.identifier.emailWong, MP: mwpik@hkucc.hku.hken_HK
dc.identifier.emailLam, WK: lamwk@hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.authorityWong, MP=rp00348en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.hkuros101795en_HK
dc.identifier.volume65en_HK
dc.identifier.spage1666en_HK

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