Journal
CLINICAL CHEMISTRY
Volume 59, Issue 1, Pages 211-224Publisher
AMER ASSOC CLINICAL CHEMISTRY
DOI: 10.1373/clinchem.2012.196014
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Funding
- Hong Kong Research Grants Council Theme-based Research Scheme [T12-CUHK05/10]
- Innovation and Technology Fund under State Key Laboratory Programme
- S.K. Yee Foundation
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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. (C) 2012 American Association for Clinical Chemistry
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