A comparison of methods for EGFR mutation testing in non-small cell lung cancer.

2.50
Hdl Handle:
http://hdl.handle.net/11287/599255
Title:
A comparison of methods for EGFR mutation testing in non-small cell lung cancer.
Authors:
Young, Elizabeth C.; Owens, Martina; Adebiyi, I; Bedenham, T; Butler, R; Callaway, J; Cranston, T; Crosby, C; Cree, I A; Dutton, L; Faulkes, C; Faulkner, C; Howard, E; Knight, J; Huang, Y; Lavender, L; Lazarou, L P; Liu, H; Mair, D; Milano, A; Sandell, S; Skinner, A; Wallace, A; Williams, M. V.; Spivey, V; Goodall, J; Frampton, J; Ellard, Sian ( 0000-0002-7620-5526 )
Abstract:
EGFR mutation testing of tumor samples is routinely performed to predict sensitivity to treatment with tyrosine kinase inhibitors for patients with non-small cell lung cancer. At least 9 different methodologies are employed in UK laboratories, and the aim of this study was to compare the sensitivity of different methods for the detection of EGFR mutations. Participating laboratories were sent coded samples with varying mutation loads (from 0% to 15%) to be tested for the p.Leu858Arg (p.L858R) missense mutation and c.2235_2249del exon 19 deletion. The p.L858R mutation and deletions within exon 19 of the EGFR gene account for ∼90% of mutation-positive cases. The 11 laboratories used their standard testing method(s) and submitted 15 sets of results for the p.L858R samples and 10 for the exon 19 deletion. The p.Leu858Arg (p.L858R) mutation was detected at levels between 1% and 7.5% by Sanger sequencing, pyrosequencing, real-time polymerase chain reaction (PCR), amplification refractory mutation system, and capillary electrophoresis single-strand conformation analysis. The c.2235_2249del mutation was detected at 1% to 5% by fragment size analysis, Sanger sequencing or real-time PCR. A mutation was detected in 24/25 (96%) of the samples tested which contained 5% mutated DNA. The 1% sensitivity claimed for commercial real-time PCR-targeted EGFR tests was achieved and our results show greater sensitivity for the Sanger sequencing and pyrosequencing screening methods compared to the 10% to 20% detection levels cited on clinical diagnostic reports. We conclude that multiple methodologies are suitable for the detection of acquired EGFR mutations.
Citation:
A comparison of methods for EGFR mutation testing in non-small cell lung cancer. 2013, 22 (4):190-5 Diagn. Mol. Pathol.
Publisher:
Wolters Kluwer
Journal:
Diagnostic molecular pathology : the American journal of surgical pathology, part B
Issue Date:
Dec-2013
URI:
http://hdl.handle.net/11287/599255
DOI:
10.1097/PDM.0b013e318294936c
PubMed ID:
24193010
Additional Links:
http://journals.lww.com/molecularpathology/pages/articleviewer.aspx?year=2013&issue=12000&article=00002&type=abstract
Type:
Journal Article; Comparative Study; Evaluation Studies; Multicenter Study
Language:
en
ISSN:
1533-4066
Appears in Collections:
pre-2014 RD&E publications; Molecular Genetics; Molecular Genetics; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorYoung, Elizabeth C.en
dc.contributor.authorOwens, Martinaen
dc.contributor.authorAdebiyi, Ien
dc.contributor.authorBedenham, Ten
dc.contributor.authorButler, Ren
dc.contributor.authorCallaway, Jen
dc.contributor.authorCranston, Ten
dc.contributor.authorCrosby, Cen
dc.contributor.authorCree, I Aen
dc.contributor.authorDutton, Len
dc.contributor.authorFaulkes, Cen
dc.contributor.authorFaulkner, Cen
dc.contributor.authorHoward, Een
dc.contributor.authorKnight, Jen
dc.contributor.authorHuang, Yen
dc.contributor.authorLavender, Len
dc.contributor.authorLazarou, L Pen
dc.contributor.authorLiu, Hen
dc.contributor.authorMair, Den
dc.contributor.authorMilano, Aen
dc.contributor.authorSandell, Sen
dc.contributor.authorSkinner, Aen
dc.contributor.authorWallace, Aen
dc.contributor.authorWilliams, M. V.en
dc.contributor.authorSpivey, Ven
dc.contributor.authorGoodall, Jen
dc.contributor.authorFrampton, Jen
dc.contributor.authorEllard, Sianen
dc.date.accessioned2016-02-25T15:04:59Zen
dc.date.available2016-02-25T15:04:59Zen
dc.date.issued2013-12en
dc.identifier.citationA comparison of methods for EGFR mutation testing in non-small cell lung cancer. 2013, 22 (4):190-5 Diagn. Mol. Pathol.en
dc.identifier.issn1533-4066en
dc.identifier.pmid24193010en
dc.identifier.doi10.1097/PDM.0b013e318294936cen
dc.identifier.urihttp://hdl.handle.net/11287/599255en
dc.description.abstractEGFR mutation testing of tumor samples is routinely performed to predict sensitivity to treatment with tyrosine kinase inhibitors for patients with non-small cell lung cancer. At least 9 different methodologies are employed in UK laboratories, and the aim of this study was to compare the sensitivity of different methods for the detection of EGFR mutations. Participating laboratories were sent coded samples with varying mutation loads (from 0% to 15%) to be tested for the p.Leu858Arg (p.L858R) missense mutation and c.2235_2249del exon 19 deletion. The p.L858R mutation and deletions within exon 19 of the EGFR gene account for ∼90% of mutation-positive cases. The 11 laboratories used their standard testing method(s) and submitted 15 sets of results for the p.L858R samples and 10 for the exon 19 deletion. The p.Leu858Arg (p.L858R) mutation was detected at levels between 1% and 7.5% by Sanger sequencing, pyrosequencing, real-time polymerase chain reaction (PCR), amplification refractory mutation system, and capillary electrophoresis single-strand conformation analysis. The c.2235_2249del mutation was detected at 1% to 5% by fragment size analysis, Sanger sequencing or real-time PCR. A mutation was detected in 24/25 (96%) of the samples tested which contained 5% mutated DNA. The 1% sensitivity claimed for commercial real-time PCR-targeted EGFR tests was achieved and our results show greater sensitivity for the Sanger sequencing and pyrosequencing screening methods compared to the 10% to 20% detection levels cited on clinical diagnostic reports. We conclude that multiple methodologies are suitable for the detection of acquired EGFR mutations.en
dc.language.isoenen
dc.publisherWolters Kluweren
dc.relation.urlhttp://journals.lww.com/molecularpathology/pages/articleviewer.aspx?year=2013&issue=12000&article=00002&type=abstracten
dc.rightsArchived with thanks to Diagnostic molecular pathology : the American journal of surgical pathology, part Ben
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleA comparison of methods for EGFR mutation testing in non-small cell lung cancer.en
dc.typeJournal Articleen
dc.typeComparative Studyen
dc.typeEvaluation Studiesen
dc.typeMulticenter Studyen
dc.identifier.journalDiagnostic molecular pathology : the American journal of surgical pathology, part Ben
dc.type.versionPublisheden

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