Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing

Clin Chem. 2013 Jan;59(1):211-24. doi: 10.1373/clinchem.2012.196014. Epub 2012 Oct 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • DNA Copy Number Variations*
  • Female
  • Genes, Neoplasm*
  • Genome*
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / genetics
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics
  • Sequence Analysis, DNA / methods*