A Pan-Canadian Validation Study for the Detection of EGFR T790M Mutation Using Circulating Tumor DNA From Peripheral Blood
| العنوان: | A Pan-Canadian Validation Study for the Detection of EGFR T790M Mutation Using Circulating Tumor DNA From Peripheral Blood |
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| المؤلفون: | Wenda L. Greer, Normand Blais, Danh Tran-Thanh, Rami Nassabein, Tracy Stockley, Tara Spence, Martin Butcher, R. Walton, Stephanie Santos, Xiao Zhang, Doug Demetrick, Shamini Selvarajah, Bryan Lo, Bekim Sadikovic, Marsha Speevak, Sophie Plante, Andrea K. Vaags, Elizabeth McCready, Darren Hamelinck, Tong Zhang, Daria Grafodatskaya, Philippe Joubert, Harriet Feilotter, Xiaoduan Weng |
| المصدر: | JTO Clinical and Research Reports, Vol 2, Iss 8, Pp 100212-(2021) Paediatrics Publications |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Liquid biopsy, business.industry, Plasma ctDNA testing, Concordance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Resistance mutation, T790M, EGFR T790M variant, Internal medicine, medicine, Non–small cell lung cancer, Digital polymerase chain reaction, business, Genotyping, Allele frequency, RC254-282, EGFR inhibitors |
| الوصف: | Introduction Genotyping circulating tumor DNA (ctDNA) is a promising noninvasive clinical tool to identify the EGFR T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing. Methods In phase 1, commercial reference standards were distributed to participating clinical laboratories, to use their existing platforms for mutation detection. Baseline performance characteristics were established using known and blinded engineered plasma samples spiked with predetermined concentrations of T790M, L858R, and exon 19 deletion variants. In phase II, peripheral blood collected from local patients with known EGFR activating mutations and progressing on treatment were assayed for the presence of EGFR variants and concordance with a clinically validated test at the reference laboratory. Results All laboratories in phase 1 detected the variants at 0.5 % and 5.0 % allele frequencies, with no false positives. In phase 2, the concordance with the reference laboratory for detection of both the primary and resistance mutation was high, with next-generation sequencing and droplet digital polymerase chain reaction exhibiting the best overall concordance. Data also suggested that the ability to detect mutations at clinically relevant limits of detection is generally not platform-specific, but rather impacted by laboratory-specific practices. Conclusions Discrepancies among sending laboratories using the same assay suggest that laboratory-specific practices may impact performance. In addition, a negative or inconclusive ctDNA test should be followed by tumor testing when possible. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2666-3643 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a822a1f06d5c0b5f9e1183019fb983bTest http://www.sciencedirect.com/science/article/pii/S2666364321000710Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3a822a1f06d5c0b5f9e1183019fb983b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 26663643 |
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