Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing

Chan, Ka‐Kui; Jiang, Peiyong; Zheng, Yama W. L.; Liao, Gary J.W.; Sun, Hao; Wong, John; Siu, Stephanie; Chan, Wing Cheong; Chan, Stephen L.; Chan, Anthony Tak-cheung; Lai, Paul B.S.; Chiu, Rossa W.̉K.; Lo, Yuk-ming Dennis

doi:10.1373/clinchem.2012.196014

Cited by 445 publications

(355 citation statements)

References 33 publications

Supporting

Mentioning

345

Contrasting

Unclassified

Order By: Relevance

“…However, this is in contrast to our own observations (14,15 ) and reports by others (2 ). Indeed, the Qiagen Mini Kit for DNA extraction limits the isolation to fragment sizes of Ն100 bp, and furthermore, the FAST-SeqS assay amplifies PCR products in the range of 124 -142 bp.…”

Section: Discussioncontrasting

confidence: 98%

“…Recent progress in the analysis of cell-free circulating tumor DNA (ctDNA) 6 now allows monitoring of tumor genomes by noninvasive means (1)(2)(3)(4)(5)(6)(7). Basically, 2 strategies to monitor ctDNA have emerged.…”

mentioning

confidence: 99%

“…Second, untargeted approaches establish genomewide patterns of copy number aberrations (CNAs) from ctDNA (2,4,15,17 ) or assess the mutation spectrum by exome sequencing from plasma DNA (7 ) (Fig. 1).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Rapid Identification of Plasma DNA Samples with Increased ctDNA Levels by a Modified FAST-SeqS Approach

Belic¹,

Koch²,

Ulz³

et al. 2015

Clinical Chemistry

111

View full text Add to dashboard Cite

BACKGROUND:Recent progress in the analysis of cellfree DNA fragments [cell-free circulating tumor DNA (ctDNA)] now allows monitoring of tumor genomes by noninvasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. The comprehensive analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. Therefore, a fast and cost-effective prescreening method to identify such plasma samples without previous knowledge about alterations in the respective tumor genome could assist in the selection of samples suitable for further extensive qualitative analysis.

show abstract

Section: Discussioncontrasting

confidence: 98%

mentioning

confidence: 99%

See 1 more Smart Citation

Rapid Identification of Plasma DNA Samples with Increased ctDNA Levels by a Modified FAST-SeqS Approach

Belic¹,

Koch²,

Ulz³

et al. 2015

Clinical Chemistry

111

View full text Add to dashboard Cite

show abstract

“…Repeated biopsies to study genomic alterations resulting from therapies are invasive, can be difficult to obtain, and may be confounded by intratumoral heterogeneity. A possible resolution to this problem is analysis of circulating tumor DNA (ctDNA) released by cancer cells into the plasma ( 20 ). Serial analysis of ctDNA can be used to track genomic evolution of metastatic cancers in response to therapy to complement invasive biopsy approaches and identify mutations associated with acquired drug resistance in advanced cancers ( 21 ), but it is unclear how this technology can be used in the routine setting of a hospital.…”

mentioning

confidence: 99%

Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma

et al. 2016

View full text Add to dashboard Cite

Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell–derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma. Significance: Although recent developments have revolutionized melanoma care, most patients still die of their disease. To improve melanoma outcomes further, we developed a powerful precision medicine platform to monitor patient responses and to identify and validate hypothesis-driven therapies for patients who do not respond, or who develop resistance to current treatments. Cancer Discov; 6(3); 286–99. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 217

show abstract

“…33 Most studies of patients with known cancer have not contained normal controls, but a limited number of targeted sequencing studies have shown some degree of mutation detection (false positives), albeit usually at a low level, in normal controls. 28,34,35 Low sensitivity to detect early-stage cancer (false negatives) is another limitation. Studies have shown sensitivities in the 30% to 60% range for early-stage tumors, and some tumor types may have a higher false-negative rate, as ctDNA appears to be released owing to apoptosis and necrosis.…”

mentioning

confidence: 99%

Review of Clinical Next-Generation Sequencing

Yohe

Thyagarajan

2017

Archives of Pathology &Amp; Laboratory Medicine

280

195

View full text Add to dashboard Cite

Context.-Next-generation sequencing (NGS) is a technology being used by many laboratories to test for inherited disorders and tumor mutations. This technology is new for many practicing pathologists, who may not be familiar with the uses, methodology, and limitations of NGS.Objective.-To familiarize pathologists with several aspects of NGS, including current and expanding uses; methodology including wet bench aspects, bioinformatics, and interpretation; validation and proficiency; limitations; and issues related to the integration of NGS data into patient care.Data Sources.-The review is based on peer-reviewed literature and personal experience using NGS in a clinical setting at a major academic center.Conclusions.-The clinical applications of NGS will increase as the technology, bioinformatics, and resources evolve to address the limitations and improve quality of results. The challenge for clinical laboratories is to ensure testing is clinically relevant, cost-effective, and can be integrated into clinical care.( As with any new technology, the use of NGS in the clinical laboratory has evolved and will continue to evolve over time. New applications for the technology continue to be developed, new bioinformatics and wet bench techniques are being developed to address current limitations and improve performance, and new knowledge regarding interpretation of rare variants is being accumulated. This article is an overview of clinical NGS, including recent trends as well as evolution that will likely occur in the near future. The review is based on peer-reviewed literature and personal experience using NGS in a clinical setting at a major academic center. The Molecular Diagnostics Laboratory at

show abstract

Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing

Abstract: BACKGROUND:Tumor-derived DNA can be found in the plasma of cancer patients. In this study, we explored the use of shotgun massively parallel sequencing (MPS) of plasma DNA from cancer patients to scan a cancer genome noninvasively.

Cited by 445 publications

References 33 publications

Rapid Identification of Plasma DNA Samples with Increased ctDNA Levels by a Modified FAST-SeqS Approach

Rapid Identification of Plasma DNA Samples with Increased ctDNA Levels by a Modified FAST-SeqS Approach

Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma

Review of Clinical Next-Generation Sequencing

Contact Info

Product

Resources

About