Giant Magnetoresistive Nanosensor Analysis of Circulating Tumor DNA Epidermal Growth Factor Receptor Mutations for Diagnosis and Therapy Response Monitoring.
BACKGROUND: Liquid biopsy circulating tumor DNA (ctDNA) mutational analysis holds great promises for precision medicine targeted therapy and more effective cancer management. However, its wide adoption is hampered by high cost and long turnaround time of sequencing assays, or by inadequate analytica...
| Publicado en: | Clinical Chemistry Vol. 67; no. 3; pp. 534 - 543 |
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| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Oxford University Press / USA
Mar2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149456225&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149456225 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00099147 10CS jtl: Clinical Chemistry issn: 00099147 maglogo: N pubinfo: dt: Mar2021 vid: 67 iid: 3 pid: 622 pub: Oxford University Press / USA artinfo: ui: 149456225 10.1093/clinchem/hvaa307 149456225 ppf: 534 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Giant Magnetoresistive Nanosensor Analysis of Circulating Tumor DNA Epidermal Growth Factor Receptor Mutations for Diagnosis and Therapy Response Monitoring. aug: au: C. Nesvet, Jared A. Antilla, Katie S. Pancirer, Danielle X. Lozano, Alexander S. Preiss, Jordan Ma, Weijie Fu, Aihua Park, Seung-Min S. Gambhir, Sanjiv C. Fan, Alice W. Neal, Joel K. Padda, Sukhmani Das, Millie Li, Tianhong A. Wakelee, Heather X. Wangd, Shan affil: Department of Chemistry, Stanford University, Stanford, CA, USA. sug: ab: BACKGROUND: Liquid biopsy circulating tumor DNA (ctDNA) mutational analysis holds great promises for precision medicine targeted therapy and more effective cancer management. However, its wide adoption is hampered by high cost and long turnaround time of sequencing assays, or by inadequate analytical sensitivity of existing portable nucleic acid tests to mutant allelic fraction in ctDNA. METHODS: We developed a ctDNA Epidermal Growth Factor Receptor (EGFR) mutational assay using giant magnetoresistive (GMR) nanosensors. This assay was validated in 36 plasma samples of non-small cell lung cancer patients with known EGFR mutations. We assessed therapy response through follow-up blood draws, determined concordance between the GMR assay and radiographic response, and ascertained progression-free survival of patients. RESULTS: The GMR assay achieved analytical sensitivities of 0.01% mutant allelic fraction. In clinical samples, the assay had 87.5% sensitivity (95% CI = 64.0-97.8%) for Exon19 deletion and 90% sensitivity (95% CI = 69.9-98.2%) for L858R mutation with 100% specificity; our assay detected T790M resistance with 96.3% specificity (95% CI - 81.7-99.8%) with 100% sensitivity. After 2 weeks of therapy, 10 patients showed disappearance of ctDNA by GMR (predicted responders), whereas 3 patients did not (predicted nonresponders). These predictions were 100% concordant with radiographic response. Kaplan-Meier analysis showed responders had significantly (P<0.0001) longer PFS compared to nonresponders (N/A vs. 12 weeks, respectively). CONCLUSIONS: The GMR assay has high diagnostic sensitivity and specificity and is well suited for detecting EGFR mutations at diagnosis and noninvasively monitoring treatment response at the point-of-care. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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