Hopkins Researchers Find Genetic Alterations Linked to Cancer in Some Blood Samples

Using a new molecular test, investigators at The Johns HopkinsUniversity School of Medicine have detected genetic mutationsspecific to cancer in blood samples of six patients with headand neck cancer. Their findings are reported in the Septemberissue of Nature Medicine.

"Although quite preliminary, these findings are interestingbecause the presence of DNA alterations in the blood appears tobe associated with large, advanced tumors and with cancer thathas spread," said lead author David Sidransky, md, associateprofessor of otolaryngology/head and neck surgery, and oncology.Sidransky cautioned that the test does not appear to be usefulas a screening test for cancer. "But it might be helpfulin patient management by identifying patients with a very poorprognosis who may benefit from aggressive therapy," he said.

The test works by identifying replication errors, or chromosomaldeletions, in the DNA of cancer cells. In this study, the investigatorsexamined DNA from patients' serum and compared this DNA patternto normal DNA from circulating white blood cells. They found geneticalterations in the serum of 6 of 21 head and neck cancer patientsthat were identical to alterations from the tumor itself.

Serum DNA Alterations Linked With Poor Outcomes

Examining disease outcomes, the researchers found that 4 of the6 patients with positive test results subsequently died of theircancer, as compared with only 3 of 15 with negative test results.The three patients who developed distant metastases were in thepositive test group, further indicating that poor outcome maybe associated with the presence of serum DNA alterations. Theseresults must be confirmed in much larger clinical trials, Sidranskysaid.

The technique used in this study was developed by Sidransky'steam and was first used to detect cancer cells in urine. The testuses a series of DNA markers to seek out genetic mutations specificto each patient's cancer. "We decided to test serum samplesbased on evidence from scientists two decades ago which pointedto increased levels of serum DNA in cancer patients," Sidranskysaid. "More recent studies suggest that cancer cells circulatingin the blood may die and release DNA, which is carried throughthe bloodstream by plasma."

In an accompanying study in Nature Medicine, a team fromSwitzerland (also coauthors of the Hopkins study) found geneticalterations in the plasma of over 70% of patients with small celllung cancer. The authors speculate that the higher presence ofalterations may be indicative of a high propensity of this cancerto spread.

In addition to Sidransky, other participants in the Hopkins studyinclude Drs. Homaira Nawroz and Wayne Koch from the Departmentof Otolaryngology-Head and Neck Cancer at Johns Hopkins, and Drs.Philippe Anker and Maurice Stroun from the Laboratory of PlantBiochemistry and Physiology at the University of Geneva in Switzerland.