Using a new molecular test, investigators at The Johns Hopkins
University School of Medicine have detected genetic mutations
specific to cancer in blood samples of six patients with head
and neck cancer. Their findings are reported in the September
issue of Nature Medicine.
"Although quite preliminary, these findings are interesting
because the presence of DNA alterations in the blood appears to
be associated with large, advanced tumors and with cancer that
has spread," said lead author David Sidransky, md, associate
professor of otolaryngology/head and neck surgery, and oncology.
Sidransky cautioned that the test does not appear to be useful
as a screening test for cancer. "But it might be helpful
in patient management by identifying patients with a very poor
prognosis who may benefit from aggressive therapy," he said.
The test works by identifying replication errors, or chromosomal
deletions, in the DNA of cancer cells. In this study, the investigators
examined DNA from patients' serum and compared this DNA pattern
to normal DNA from circulating white blood cells. They found genetic
alterations in the serum of 6 of 21 head and neck cancer patients
that were identical to alterations from the tumor itself.
Serum DNA Alterations Linked With Poor Outcomes
Examining disease outcomes, the researchers found that 4 of the
6 patients with positive test results subsequently died of their
cancer, as compared with only 3 of 15 with negative test results.
The three patients who developed distant metastases were in the
positive test group, further indicating that poor outcome may
be associated with the presence of serum DNA alterations. These
results must be confirmed in much larger clinical trials, Sidransky
The technique used in this study was developed by Sidransky's
team and was first used to detect cancer cells in urine. The test
uses a series of DNA markers to seek out genetic mutations specific
to each patient's cancer. "We decided to test serum samples
based on evidence from scientists two decades ago which pointed
to increased levels of serum DNA in cancer patients," Sidransky
said. "More recent studies suggest that cancer cells circulating
in the blood may die and release DNA, which is carried through
the bloodstream by plasma."
In an accompanying study in Nature Medicine, a team from
Switzerland (also coauthors of the Hopkins study) found genetic
alterations in the plasma of over 70% of patients with small cell
lung cancer. The authors speculate that the higher presence of
alterations may be indicative of a high propensity of this cancer
In addition to Sidransky, other participants in the Hopkins study
include Drs. Homaira Nawroz and Wayne Koch from the Department
of Otolaryngology-Head and Neck Cancer at Johns Hopkins, and Drs.
Philippe Anker and Maurice Stroun from the Laboratory of Plant
Biochemistry and Physiology at the University of Geneva in Switzerland.