Genomic Analysis of Plasma Cell-Free DNA in Patients With Cancer

Oxnard, Geoffrey R.; Paweletz, Cloud P.; Sholl, Lynette M.

doi:10.1001/jamaoncol.2016.2835

Cited by 64 publications

(45 citation statements)

References 7 publications

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“…8,9 However, it is challenging to perform multiplex testing and detect fusions using digital PCR. 10 In contrast, plasma genotyping by next-generation sequencing (NGS) can simultaneously interrogate multiple genes and identify a broad range of molecular alterations, including chromosomal rearrangements. 10 NGS may, therefore, be optimally positioned for characterizing TKI resistance in ALK -rearranged (i.e., ALK-positive) NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors Through Longitudinal Analysis of Circulating Tumor DNA

Dagogo‐Jack¹,

Brannon²,

Ferris³

et al. 2018

JCO Precision Oncology

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Purpose ALK rearrangements predict for sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, responses to ALK TKIs are generally short-lived. Serial molecular analysis is an informative strategy for identifying genetic mediators of resistance. Although multiple studies support the clinical benefits of repeat tissue sampling, the clinical utility of longitudinal circulating tumor DNA analysis has not been established in ALK-positive lung cancer. Methods Using a 566-gene hybrid-capture next-generation sequencing (NGS) assay, we performed longitudinal analysis of plasma specimens from 22 ALK-positive patients with acquired resistance to ALK TKIs to track the evolution of resistance during treatment. To determine tissue-plasma concordance, we compared plasma findings to results of repeat biopsies. Results At progression, we detected an ALK fusion in plasma from 19 (86%) of 22 patients, and identified ALK resistance mutations in plasma specimens from 11 (50%) patients. There was 100% agreement between tissue- and plasma-detected ALK fusions. Among 16 cases where contemporaneous plasma and tissue specimens were available, we observed 100% concordance between ALK mutation calls. ALK mutations emerged and disappeared during treatment with sequential ALK TKIs, suggesting that plasma mutation profiles were dependent on the specific TKI administered. ALK G1202R, the most frequent plasma mutation detected after progression on a second-generation TKI, was consistently suppressed during treatment with lorlatinib. Conclusions Plasma genotyping by NGS is an effective method for detecting ALK fusions and ALK mutations in patients progressing on ALK TKIs. The correlation between plasma ALK mutations and response to distinct ALK TKIs highlights the potential for plasma analysis to guide selection of ALK-directed therapies.

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Section: Introductionmentioning

confidence: 99%

Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors Through Longitudinal Analysis of Circulating Tumor DNA

Dagogo‐Jack¹,

Brannon²,

Ferris³

et al. 2018

JCO Precision Oncology

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“…In recent years, it has become well established that patients with malignant tumors may have circulating cell-free tumor DNA, which is becoming increasingly used for clinical disease screening and monitoring. 13,14 Thus, it is theoretically possible that, in a donor with an occult malignant tumor, plasma thrombin could be contaminated with cell-free tumor DNA, which could be detected by high-sensitivity methods, such as nextgeneration sequencing. Another common cell block preparation method-Cellient-is reported to achieve good results for specimens with low cellularity.…”

Section: Discussionmentioning

confidence: 99%

Novel Modification of HistoGel-Based Cell Block Preparation Method: Improved Sufficiency for Molecular Studies

Rekhtman¹,

Buonocore²,

Rudomina³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Cell block preparation methods vary substantially across institutions and are frequently suboptimal. The growing importance of biomarker testing in the era of targeted therapies makes optimization of cell block preparation critically important.Objective.-To develop an improved cell block preparation method.Design.-Ex vivo fine-needle aspirates and scrapes from surgically resected tumors were used to develop an improved HistoGel (Thermo Fisher Scientific, Waltham, Massachusetts)-based cell block preparation method. Cellularity yield with the new versus the standard method was assessed in ex vivo split samples and in consecutive clinical fine-needle aspirates processed before (n ¼ 100) and after (n ¼ 100) the new method was implemented in our laboratory. Sufficiency of cell block material for potential molecular studies was estimated by manual cell quantitation.Results.-The key modification in the new method was pretreatment of the pelleted cells with 95% ethanol before the addition of HistoGel (HistoGel þ ethanol method). In addition, we optimized the melting conditions of HistoGel and added a dark, inorganic marker to the cell pellets to highlight the desired level of sectioning during microtomy. Cell blocks from ex vivo split samples showed that the HistoGel þ ethanol method yielded, on average, an 8.3-fold (range, 1-20) greater cellularity compared with the standard HistoGel-only method. After the switch from the standard HistoGel method to the modified method in our clinical practice, sufficiency of positive fine-needle aspirates for some molecular studies increased from 72% to 97% (P ¼ .002).Conclusions.-We describe a simple and readily adoptable modification of the HistoGel method, which results in substantial improvement in cell capture in cell blocks, leading to a significant increase in sufficiency for potential molecular and other ancillary studies.

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“…In terms of detection methods, circulating miRNA is based on high-throughput sequencing, miRNA chips, northern blot, qRT-PCR, [110][111][112][113][114][115][116][117] modification, but the disadvantage is the cumbersome and expensive operation. 86,87 Furthermore, qRT-PCR is a gold standard for quantitative detection of miRNA, which can perform relative quantitative and absolute quantitative detection of miRNA and can detect the expression level of miRNA more intuitively.…”

Section: Challenges Of Circulating Mirna As a Biomarkermentioning

confidence: 99%

Circulating miRNA or circulating DNA—Potential biomarkers for organ transplant rejection

Huo

Zhou

Cooper

et al. 2018

Xenotransplantation

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Accurate and timely diagnosis of transplant rejection is essential for the long‐term survival of solid‐organ transplant recipients. Biopsy is the “gold standard” for the diagnosis of rejection, but this approach is a time‐consuming, expensive, and invasive process. An efficient, cheap, and noninvasive tool for monitoring of immune rejection is urgently needed. Circulating miRNA and circulating DNA can be easily amplified and quantified by PCR which could be potential biomarkers for monitoring organ survival and/or immune rejection. In this review, we briefly introduce the origins and characteristics of circulating miRNA and circulating DNA. Furthermore, we review their clinical application and potential as noninvasive biomarkers for rejection in organ transplantation. Finally, we sum up their potential as biomarkers, which may help scientists and surgeons choose the proper biomarker for routine assays.

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Genomic Analysis of Plasma Cell-Free DNA in Patients With Cancer

Cited by 64 publications

References 7 publications

Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors Through Longitudinal Analysis of Circulating Tumor DNA

Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors Through Longitudinal Analysis of Circulating Tumor DNA

Novel Modification of HistoGel-Based Cell Block Preparation Method: Improved Sufficiency for Molecular Studies

Circulating miRNA or circulating DNA—Potential biomarkers for organ transplant rejection

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