Yang, Wei;
Christensen, Mari;
Chan, Jennifer K.;
Tsai, Julie;
Patten, Nancy;
Tran, Ha B.;
Hillman, Grant R.;
Tai, Yu Chuan;
Bogard, Patrick;
Litterst, Claudia M.;
Brophy, Victoria H.;
Newton, Nick;
Nelson, Christopher D.;
Pattje, Wouter J.
Abstract 5156: Multiplexed EGFR mutation detection with C797S and T790M allelic context using six-color digital PCR
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Medientyp:
E-Artikel
Titel:
Abstract 5156: Multiplexed EGFR mutation detection with C797S and T790M allelic context using six-color digital PCR
Beteiligte:
Yang, Wei;
Christensen, Mari;
Chan, Jennifer K.;
Tsai, Julie;
Patten, Nancy;
Tran, Ha B.;
Hillman, Grant R.;
Tai, Yu Chuan;
Bogard, Patrick;
Litterst, Claudia M.;
Brophy, Victoria H.;
Newton, Nick;
Nelson, Christopher D.;
Pattje, Wouter J.
Erschienen:
American Association for Cancer Research (AACR), 2022
Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Non-small cell lung cancer (NSCLC) patients harboring activating mutations in epidermal growth factor receptor (EGFR) are benefited from Tyrosine Kinase Inhibitor (TKI) targeted therapy. However, more than 50% of patients receiving the first or second generations of TKI develop a resistance mutation, EGFR-T790M, and they will need to switch to the third-generation TKI (Osimertinib). Upon treatment, a second acquired mutation, EGFR-C797S, leads to the resistance to Osimertinib. If the C797S and T790M mutations are located in trans, a combination of the first and third-generation of TKI(s) may offer some benefit to the patient. The impact of the allelic context to the subsequent treatment is yet to be established and thus an assay identifying C797S and T790M allelic context may serve as a useful research tool. In recent years, digital PCR has emerged to be an ultra-sensitive method in non-invasive identification and monitoring of cancer mutations. However, compared to qPCR and NGS methods, current digital PCR assays are limited by the number of biomarkers that can be incorporated in a single assay and the maximum sample volume that can be screened in one test. In this study, we describe a multiplex digital PCR assay for quantitative detection of EGFR sensitizing and resistance mutations, and identification of C797S and T790M allelic context, using a 6-color digital PCR system that allows high sample volume utilization. The sensitivity and specificity of this multiplex dPCR assay were tested using a panel of contrived cell-free DNA samples. Individual mutations can be detected at as low as 0.2% fractional abundance level. Furthermore, we compared the performance of the multiplex with the 2-color droplet digital PCR Expert Design Assays on the Bio-Rad QX200 ddPCR system, using a commercial multiplex cfDNA reference standard set. The multiplexed EGFR mutation assay on the 6-color Digital LightCycler® System is a promising method for rapid and sensitive monitoring of EGFR mutations in cell-free DNA.</jats:p>
<jats:p>Citation Format: Wei Yang, Mari Christensen, Jennifer K. Chan, Julie Tsai, Nancy Patten, Ha B. Tran, Grant R. Hillman, Yu Chuan Tai, Patrick Bogard, Claudia M. Litterst, Victoria H. Brophy, Nick Newton, Christopher D. Nelson, Wouter J. Pattje. Multiplexed EGFR mutation detection with C797S and T790M allelic context using six-color digital PCR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5156.</jats:p>