Individual Prognosis Through Genetic Analysis of Brain Tumor Cells

“This finding is a step forward for the benefit of the patient,” says Dr. Stefan Pfister, who is pleased about the results jointly with his colleagues, Professor Andrey Korshunov and Dr. Hendrik Witt of DKFZ and Heidelberg University Hospitals. “Now we can develop new and individual treatment approaches for patients with biologically different ependymomas. We can use the specific alterations in the chromosomes as markers which indicate the degree of intensity needed for treating different patient groups.”

The researchers studied tumor material of 292 patients suffering from ependymoma, the second most frequent brain tumor in children. The study included only patients with established WHO tumor grades II and III. However, this ependymoma classification hardly provides any indication of how difficult treatment of the disease will be.

Surgery is the first form of treatment for ependymoma patients. It may be difficult to remove the tumor completely, since ependymomas frequently grow close to the brain stem or other vital brain structures. The traditional postoperative treatment for younger children is chemotherapy, while older children receive radiotherapy. The age limit in the study presented was four years, because detrimental late effects of irradiation on the developing brain in very young children were feared.

The researchers studied the tumor cells removed, comparing them with healthy cells. They found characteristic alterations in the chromosomes, the carriers of genetic material, of the brain tumor cells. They regularly found gains or losses of whole chromosomes or chromosome regions. The investigators proceeded to compare the prognostic value of these aberrations with respect to survival with known prognostic factors. These include recurrence of disease, age at diagnosis, gender, position of tumor in the brain, WHO tumor grade and whether or not it was possible to remove the tumor completely by surgery.

The researchers found out that, besides a young age at diagnosis, the knowledge of individual alterations in the genetic material of tumor cells facilitates very accurate predictions about disease progression. Thus, gains on the long arm of chromosome 1 as well as the loss of tumor-suppressing genes are associated with a rather poor response to treatment so that it is important to find new or additional treatment options for these patients. On the other hand, complete loss of chromosome 6 or gains on chromosomes 9, 15 or 18 were associated with longer survival of the patients. Further investigations will show whether doctors may spare these patients some stressful treatments.

A picture for this press release is available on the Internet at:
http://www.dkfz.de/de/presse/pressemitteilungen/2010/images/Pfister_homozygous_deletion.jpg

Picture caption: Fluorescence image of cells of a high-risk brain tumor (ependymoma). Scientists recognize a loss of genetic material because there are only single red and green dots. In a healthy cell, two signals of each color (= 2 copies of each specific DNA) would be expected.

Literature:
A. Korshunov et al: Molecular Staging of Intracranial Ependymoma in Children and Adults. J Clin Oncol 28. DOI:10.1200/JCO.2009.27.3359