Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing
K.C. Allen Chan,Peiyong Jiang,Yama W. L. Zheng,Gary J. W. Liao,Hao Sun,John Wong,Shing Shun N. Siu,Wing Cheong Chan,Stephen L. Chan,Anthony T.C. Chan,Paul B.S. Lai,Rossa W.K. Chiu,Yuk Ming Dennis Lo +12 more
TLDR
This study explored the use of shotgun massively parallel sequencing of plasma DNA from cancer patients to scan a cancer genome noninvasively and showed that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity.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.
METHODS: Four hepatocellular carcinoma patients and a patient with synchronous breast and ovarian cancers were recruited. DNA was extracted from the tumor tissues, and the preoperative and postoperative plasma samples of these patients were analyzed with shotgun MPS.
RESULTS: We achieved the genomewide profiling of copy number aberrations and point mutations in the plasma of the cancer patients. By detecting and quantifying the genomewide aggregated allelic loss and point mutations, we determined the fractional concentrations of tumor-derived DNA in plasma and correlated these values with tumor size and surgical treatment. We also demonstrated the potential utility of this approach for the analysis of complex oncologic scenarios by studying the patient with 2 synchronous cancers. Through the use of multiregional sequencing of tumoral tissues and shotgun sequencing of plasma DNA, we have shown that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity.
CONCLUSIONS: Shotgun DNA sequencing of plasma is a potentially powerful tool for cancer detection, monitoring, and research.read more
Citations
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Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer
Sarah-Jane Dawson,Dana W.Y. Tsui,Muhammed Murtaza,Heather Biggs,Oscar M. Rueda,Suet-Feung Chin,Mark J Dunning,Davina Gale,Tim Forshew,Betania Mahler-Araujo,Sabrina Rajan,Sean Humphray,Jennifer Becq,David Halsall,Matthew G. Wallis,David Bentley,Carlos Caldas,Nitzan Rosenfeld +17 more
TL;DR: This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer.
Journal ArticleDOI
Liquid Biopsies: Genotyping Circulating Tumor DNA
Luis A. Diaz,Alberto Bardelli +1 more
TL;DR: The ability to detect and quantify tumor mutations has proven effective in tracking tumor dynamics in real time as well as serving as a liquid biopsy that can be used for a variety of clinical and investigational applications not previously possible.
Journal ArticleDOI
An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage
Aaron M. Newman,Scott V. Bratman,Jacqueline To,Jacob Wynne,Neville Eclov,Leslie A. Modlin,Chih Long Liu,Joel W. Neal,Heather A. Wakelee,Robert E. Merritt,Joseph B. Shrager,Billy W. Loo,Ash A. Alizadeh,Maximilian Diehn +13 more
TL;DR: It is envisioned that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.
Journal ArticleDOI
Liquid biopsies come of age: towards implementation of circulating tumour DNA
Jonathan C. M. Wan,Charles E. Massie,Javier Garcia-Corbacho,Florent Mouliere,James D. Brenton,Carlos Caldas,Simon Pacey,Richard D. Baird,Nitzan Rosenfeld +8 more
TL;DR: The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA.
Journal ArticleDOI
Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA
Muhammed Murtaza,Sarah-Jane Dawson,Dana W.Y. Tsui,Davina Gale,Tim Forshew,Anna M. Piskorz,Christine Parkinson,Suet-Feung Chin,Zoya Kingsbury,Alvin Wong,Francesco Marass,Sean Humphray,James Hadfield,David Bentley,Tan Min Chin,Tan Min Chin,James D. Brenton,Carlos Caldas,Nitzan Rosenfeld +18 more
TL;DR: Serial analysis of cancer genomes in plasma constitutes a new paradigm for the study of clonal evolution in human cancers, establishing proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify mutations associated with acquired drug resistance in advanced cancers.
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