Update on<i>Epidermal Growth Factor Receptor</i>Mutations in Non–Small Cell Lung Cancer

Riely, Gregory J.; Politi, Katerina; Miller, Vincent A.; Pao, William

doi:10.1158/1078-0432.ccr-06-0658

Cited by 342 publications

(305 citation statements)

References 106 publications

(29 reference statements)

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“…34 The distribution of EGFR mutation types identified in our cohort was consistent with other series, with most mutations being in-frame exon 19 deletions and the L858R point mutations in exon 21. 20,25,26,35 These 2 most frequent EGFR mutations have been consistently associated with EGFR-TKI responsiveness. 36,37 Among the individual genotype subgroups in our patient population, the frequency of a PR or SD was significantly higher among patients with an exon 19 deletion mutation compared with those with exon 21 point mutations or no detectable mutation.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

Cohen

Agulnik

Ang

et al. 2010

Cancer

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BACKGROUND:Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) in patients with nonsmall cell lung cancer (NSCLC).METHODS:The authors tested the possibility that nucleotide sequencing may be poorly suited for detection of mutations in tumor samples and found that denaturing high‐performance liquid chromatography (dHPLC) was an efficient and more sensitive method for screening.RESULTS:These results suggested that some reports based on standard DNA sequencing techniques may have underestimated mutation rates. In the present report, the authors examined the relationship between the presence and type of EGFR mutations detected by dHPLC and various clinicopathologic features of NSCLC, including response to therapy with EGFR‐TKI. Among 251 patients with advanced disease, 100 individuals received EGFR‐TKI. Those whose tumors harbored a detectable EGFR kinase mutation were much more likely to have a partial response (PR) or stable disease (SD) with EGFR‐TKI therapy than patients whose tumor contained no mutation (80% vs 35%; P = .001). Among the individual genotype subgroups, the frequency of a PR or SD was significantly different between patients with an exon 19 deletion compared with those with no detectable mutation (86% vs 35%; P < .001). Furthermore, patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend toward better EGFR‐TKI response (86% vs 67%; P = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation.CONCLUSIONS:Our findings warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types. Cancer 2010. © 2010 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

Cohen

Agulnik

Ang

et al. 2010

Cancer

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“…5,6,14,63,64 In adenocarcinomas, the majority of mutations have been identified in exons 18-21 of the EGFR gene. 9,65,66 These mutations can be roughly classified into three major categories: in-frame deletions in exon 19, insertion mutations in exon 20, and missense mutations in exons 18-21 ( Figure 2).…”

Section: Egfr Mutationsmentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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“…Exon 19 deletion and exon 21 L858R substitution account for 85-90% of the drug-sensitive EGFR mutations seen in NSCLC (Riely et al, 2006;Sakurada et al, 2006). The mutations are more common in adenocarcinomas, in persons of East Asian ethnicity, women and in never smokers.…”

Section: Egfr Mutations As Biomarkersmentioning

confidence: 99%

Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

2009

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Update onEpidermal Growth Factor ReceptorMutations in Non–Small Cell Lung Cancer

Cited by 342 publications

References 106 publications

Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

Molecular pathology of lung cancer: key to personalized medicine

Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

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