Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing

Rebecca J. Leary, Mark Sausen, Isaac Kinde, Nickolas Papadopoulos, John D. Carpten, David Craig, Joyce O'Shaughnessy, Kenneth W. Kinzler, Giovanni Parmigiani, Bert Vogelstein, Luis A. Diaz, Victor E. Velculescu

Research output: Contribution to journalArticlepeer-review


Clinical management of cancer patients could be improved through the development of noninvasive approaches for the detection of incipient, residual, and recurrent tumors. We describe an approach to directly identify tumor-derived chromosomal alterations through analysis of circulating cell-free DNA from cancer patients. Whole-genome analyses of DNA from the plasma of 10 colorectal and breast cancer patients and 10 healthy individuals with massively parallel sequencing identified, in all patients, structural alterations that were not present in plasma DNA from healthy subjects. Detected alterations comprised chromosomal copy number changes and rearrangements, including amplification of cancer driver genes such as ERBB2 and CDK6. The level of circulating tumor DNA in the cancer patients ranged from 1.4 to 47.9%. The sensitivity and specificity of this approach are dependent on the amount of sequence data obtained and are derived from the fact that most cancers harbor multiple chromosomal alterations, each of which is unlikely to be present in normal cells. Given that chromosomal abnormalities are present in nearly all human cancers, this approach represents a useful method for the noninvasive detection of human tumors that is not dependent on the availability of tumor biopsies.

Original languageEnglish (US)
Article number162ra154
JournalScience translational medicine
Issue number162
StatePublished - Nov 28 2012

ASJC Scopus subject areas

  • Medicine(all)


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