Article: EGFR array: Uses in the detection of plasma EGFR mutations in non-small cell lung cancer patients

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TitleEGFR array: Uses in the detection of plasma EGFR mutations in non-small cell lung cancer patients
AuthorsYam, I1
Lam, DCL1
Chan, K1
ChungMan Ho, J1
Ip, M1
Lam, WK1
Chan, TK1
Chan, V1
KeywordsEGFR array
Follow-up
Non-small-cell lung cancer
Plasma EGFR mutations
Tyrosine kinase inhibitor therapy
Issue Date2012
PublisherLippincott Williams & Wilkins.
CitationJournal Of Thoracic Oncology, 2012, v. 7 n. 7, p. 1131-1140 [How to Cite?]
DOI: http://dx.doi.org/10.1097/JTO.0b013e3182558198
AbstractINTRODUCTION: We aim to develop a simple and sensitive array-based method for the detection of epidermal growth factor receptor (EGFR) gene mutations in the plasma of non-small-cell lung cancer patients and determine its use in the follow-up of those on tyrosine-kinase inhibitor (TKI) therapy. METHOD: DNA from 100 μl of plasma was amplified in the presence of peptide nucleic acid clamp to provide single-stranded template for the allele-specific arrayed primer extension reaction, incorporating cyanine-5-deoxycytidine triphosphate in the newly synthesized strands. The fluorescent product was visualized by laser at 670 nm. RESULTS: Eleven different types of EGFR TKI drug-sensitive mutants (SM) were identified in plasma-DNA from 46 of 51 patients. Five patients carried only wild-type sequence. Plasma-DNA finding was concordant in 36 of 37 cases with tumor-sequencing data. This method could detect as little as 62.5 copies of mutant L858R; 125 copies of E709K + G719A or 625 copies of del 746-750 in the presence of 100,000 copies of wild-type EGFR. In 21 patients on longitudinal follow-up for up to 18 months, SM was found in all initial plasma samples, except for three samples collected after recent chemotherapy. Nine of 16 patients (56%) who responded to TKI had undetectable plasma EGFR mutant. SM was present concurrently with drug-resistant mutant in 44% of patients with disease progression while on TKI, the remaining 56% might have other mechanisms of resistance. CONCLUSION: The EGFR array provides a sensitive, inexpensive, and robust method for monitoring non-small-cell lung cancer patients' response to TKI, and obviates the need of repeated lung biopsy. Copyright © 2012 by the International Association for the Study of Lung Cancer.
ISSN1556-0864
2011 Impact Factor: 3.661
2011 SCImago Journal Rankings: 0.337
DOIhttp://dx.doi.org/10.1097/JTO.0b013e3182558198
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorYam, I
dc.contributor.authorLam, DCL
dc.contributor.authorChan, K
dc.contributor.authorChungMan Ho, J
dc.contributor.authorIp, M
dc.contributor.authorLam, WK
dc.contributor.authorChan, TK
dc.contributor.authorChan, V
dc.date.accessioned2012-08-16T05:53:26Z
dc.date.available2012-08-16T05:53:26Z
dc.date.issued2012
dc.description.abstractINTRODUCTION: We aim to develop a simple and sensitive array-based method for the detection of epidermal growth factor receptor (EGFR) gene mutations in the plasma of non-small-cell lung cancer patients and determine its use in the follow-up of those on tyrosine-kinase inhibitor (TKI) therapy. METHOD: DNA from 100 μl of plasma was amplified in the presence of peptide nucleic acid clamp to provide single-stranded template for the allele-specific arrayed primer extension reaction, incorporating cyanine-5-deoxycytidine triphosphate in the newly synthesized strands. The fluorescent product was visualized by laser at 670 nm. RESULTS: Eleven different types of EGFR TKI drug-sensitive mutants (SM) were identified in plasma-DNA from 46 of 51 patients. Five patients carried only wild-type sequence. Plasma-DNA finding was concordant in 36 of 37 cases with tumor-sequencing data. This method could detect as little as 62.5 copies of mutant L858R; 125 copies of E709K + G719A or 625 copies of del 746-750 in the presence of 100,000 copies of wild-type EGFR. In 21 patients on longitudinal follow-up for up to 18 months, SM was found in all initial plasma samples, except for three samples collected after recent chemotherapy. Nine of 16 patients (56%) who responded to TKI had undetectable plasma EGFR mutant. SM was present concurrently with drug-resistant mutant in 44% of patients with disease progression while on TKI, the remaining 56% might have other mechanisms of resistance. CONCLUSION: The EGFR array provides a sensitive, inexpensive, and robust method for monitoring non-small-cell lung cancer patients' response to TKI, and obviates the need of repeated lung biopsy. Copyright © 2012 by the International Association for the Study of Lung Cancer.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Thoracic Oncology, 2012, v. 7 n. 7, p. 1131-1140 [How to Cite?]
DOI: http://dx.doi.org/10.1097/JTO.0b013e3182558198
dc.identifier.doihttp://dx.doi.org/10.1097/JTO.0b013e3182558198
dc.identifier.epage1140
dc.identifier.hkuros202205
dc.identifier.issn1556-0864
2011 Impact Factor: 3.661
2011 SCImago Journal Rankings: 0.337
dc.identifier.issue7
dc.identifier.pmid22610259
dc.identifier.scopuseid_2-s2.0-84862893803
dc.identifier.spage1131
dc.identifier.urihttp://hdl.handle.net/10722/159617
dc.identifier.volume7
dc.languageeng
dc.publisherLippincott Williams & Wilkins.
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Thoracic Oncology
dc.relation.referencesReferences in Scopus
dc.subject.meshCarcinoma, Non-Small-Cell Lung - blood - genetics - pathology
dc.subject.meshDNA, Neoplasm - blood - genetics
dc.subject.meshMutation - genetics
dc.subject.meshReceptor, Epidermal Growth Factor - genetics
dc.subject.meshTumor Markers, Biological - blood - genetics
dc.subjectEGFR array
dc.subjectFollow-up
dc.subjectNon-small-cell lung cancer
dc.subjectPlasma EGFR mutations
dc.subjectTyrosine kinase inhibitor therapy
dc.titleEGFR array: Uses in the detection of plasma EGFR mutations in non-small cell lung cancer patients
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong