Sequencing healthy tissue provides an essential reference point for tumor genome.

A study in the April 15 edition of Science Translational Medicine, conducted by Personal Genome Diagnostics (PGDx), shows that several of the genetic alterations identified via tumor-only sequencing are not associated with the cancer. These alterations are actually due to germline mutations and available in healthy cells as well. The study was conducted by PGDx scientists working in collaboration with company co-founders Dr. Victor Velculescu and Dr. Luis Diaz, Jr. and their colleagues at Johns Hopkins University.

The high rate of false positives reported from a pool of 815 patients reenforces the need to sequence ‘healthy’ tissue samples as well as tumor samples. Nearly half of the patients analyzed were found to have tumor-only related false positives. With a large proportion of these being in actionable locations. Such false positives, may have significant implications as we move towards increasingly stratified treatments.


Sian Jones, PhD, Vice President of Genome Sciences at PGDx and a co-author of the study, commented, “We knew from our pioneering whole exome analyses of cancer patients that a significant number of the genetic alterations that were thought to be associated with tumors were also present in the inherited germline DNA. By comparing tumor DNA to DNA from normal tissue, we were able to separate out those genetic alterations that are truly tumor-specific. Accurately identifying tumor-specific alterations is essential to realizing the potential of personalized medicine to achieve better treatment outcomes. As a result of this work, we decided to include the option to analyze both normal and tumor tissue DNA when we launched our CancerSelectTM targeted gene panel, which is designed to detect those genetic alterations in the individual’s cancer that are most relevant to optimizing treatment. The study published today with our colleagues at Johns Hopkins University is a powerful validation of that decision.”