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New tumor markers determine therapy intensity
March 18, 2009Genetic aberrations in childhood brain tumors provide precise information on the course of the disease; Heidelberg researchers publish in the Journal of Clinical Oncology
Characteristic changes in the DNA of medulloblastoma, the most frequent malignant brain tumor in childhood, indicate precisely how aggressively the tumor will continue to spread and what the chances of disease relapse are. Researchers at the Center for Pediatric and Adolescent Medicine at the Heidelberg University Hospital and the German Cancer Research Center have discovered this correlation. With this new set of tumor markers, the intensity of treatment can be adjusted individually and the potentially damaging effects reduced. The results have now been published online in the prestigious Journal of Clinical Oncology.
Medulloblastoma is the most frequent childhood brain tumor
The most common malignant brain tumor in childhood is the medulloblastoma - every year, more than 100 children in Germany develop this tumor of the cerebellum and some 30-40 children die from it. The first symptoms generally appear at primary school age, but the tumor, which can already arise during embryonal development, can also occur in babies and toddlers. Aggressive radiation and chemotherapy regimens after surgery can permanently damage the brain of the growing child, for example, leading to coordination disorders and limited growth.
"Using the characteristic changes in the genetic makeup of medulloblastoma, we can predict more accurately than with conventional methods how a patient will respond to therapy and how great the risk is that the tumor will return after surgery and subsequent radiation and chemotherapy," explained Dr. Stefan Pfister, who works with his team in the department of pediatric oncology at the Center for Pediatric and Adolescent Medicine (Medical Director: Professor Dr. Dr. Andreas Kulozik) and in the department of molecular genetics at the German Cancer Research Center (Director: Professor Dr. Peter Lichter). Thus far, oncologists could estimate this risk only on the basis of histology findings, age at diagnosis, residual tumor after surgery, and existence of metastases at diagnosis.
Patients with a poor prognosis can be treated more intensively
Stefan Pfister and his research group "Molecular Genetics of Pediatric Brain Tumors" first described the new tumor markers in the medulloblastoma in 2007. For the current study, he examined tumor samples from 340 patients and compared the documented course of disease with genetic aberrations in the tumor DNA. Aberrations were seen at the chromosome level, the units in which the entire genetic information is distributed and contained. Each chromosome contains large amounts of genetic information; the entire genetic material of humans is distributed in 23 such portions, each of which is usually present in two copies (2 x 23 chromosomes). Stefan Pfister discovered that if entire segments of chromosomes number 6 and 17 are present in three copies (instead of the usual 2 copies) in the genetic material of the brain tumors, the patient's prognosis is poor. If however, one copy of chromosome 6 is missing in the tumor, the patients in the collective observed always survived. The combination of these and other characteristics led to a classification of the patients in a total of five groups requiring varying levels of intensity in treatment.
"With these markers, we can reliably identify patients with a poor prognosis and treat them more intensely from the start," said Dr. Stefan Pfister. "At the same time, we can reduce the treatment intensity for patients who will presumably respond especially well to radiation and chemotherapy. We can thus reduce consequential damage and the risk of secondary malignancies."
Another advantage of the new markers - the test is very robust and can be carried out within 48 hours in any neuropathology laboratory on tissue samples conventionally preserved in paraffin.
BMBF promotes the search for other tumor markers
The prospective validation of these markers in an independent patient cohort and the search for the simplest and most reliable methods of analysis is now the goal of a project promoted by the Federal Ministry for Education and Research (BMBF) entitled "Molecular Diagnostics," in which the university hospitals of Bonn, Mainz, Düsseldorf, Würzburg, and Heidelberg as well as the German Cancer Research Center in Heidelberg are participating under the coordination of Dr. Stefan Pfister.
University Hospital Heidelberg
The most common malignant brain tumor in childhood is the medulloblastoma - every year, more than 100 children in Germany develop this tumor of the cerebellum and some 30-40 children die from it. The first symptoms generally appear at primary school age, but the tumor, which can already arise during embryonal development, can also occur in babies and toddlers. Aggressive radiation and chemotherapy regimens after surgery can permanently damage the brain of the growing child, for example, leading to coordination disorders and limited growth.
"Using the characteristic changes in the genetic makeup of medulloblastoma, we can predict more accurately than with conventional methods how a patient will respond to therapy and how great the risk is that the tumor will return after surgery and subsequent radiation and chemotherapy," explained Dr. Stefan Pfister, who works with his team in the department of pediatric oncology at the Center for Pediatric and Adolescent Medicine (Medical Director: Professor Dr. Dr. Andreas Kulozik) and in the department of molecular genetics at the German Cancer Research Center (Director: Professor Dr. Peter Lichter). Thus far, oncologists could estimate this risk only on the basis of histology findings, age at diagnosis, residual tumor after surgery, and existence of metastases at diagnosis.
Patients with a poor prognosis can be treated more intensively
Stefan Pfister and his research group "Molecular Genetics of Pediatric Brain Tumors" first described the new tumor markers in the medulloblastoma in 2007. For the current study, he examined tumor samples from 340 patients and compared the documented course of disease with genetic aberrations in the tumor DNA. Aberrations were seen at the chromosome level, the units in which the entire genetic information is distributed and contained. Each chromosome contains large amounts of genetic information; the entire genetic material of humans is distributed in 23 such portions, each of which is usually present in two copies (2 x 23 chromosomes). Stefan Pfister discovered that if entire segments of chromosomes number 6 and 17 are present in three copies (instead of the usual 2 copies) in the genetic material of the brain tumors, the patient's prognosis is poor. If however, one copy of chromosome 6 is missing in the tumor, the patients in the collective observed always survived. The combination of these and other characteristics led to a classification of the patients in a total of five groups requiring varying levels of intensity in treatment.
"With these markers, we can reliably identify patients with a poor prognosis and treat them more intensely from the start," said Dr. Stefan Pfister. "At the same time, we can reduce the treatment intensity for patients who will presumably respond especially well to radiation and chemotherapy. We can thus reduce consequential damage and the risk of secondary malignancies."
Another advantage of the new markers - the test is very robust and can be carried out within 48 hours in any neuropathology laboratory on tissue samples conventionally preserved in paraffin.
BMBF promotes the search for other tumor markers
The prospective validation of these markers in an independent patient cohort and the search for the simplest and most reliable methods of analysis is now the goal of a project promoted by the Federal Ministry for Education and Research (BMBF) entitled "Molecular Diagnostics," in which the university hospitals of Bonn, Mainz, Düsseldorf, Würzburg, and Heidelberg as well as the German Cancer Research Center in Heidelberg are participating under the coordination of Dr. Stefan Pfister.
University Hospital Heidelberg
Medulloblastoma Current Events and Medulloblastoma News RSSWeizmann Institute Scientists Discover A New Protein Partnership That Leads to Pediatric Tumor Regression
Why are some pediatric cancers able to spontaneously regress? Prof. Michael Fainzilber and his team of the Weizmann Institute's Biological Chemistry Department seem to have unexpectedly found part of the answer.
Researchers discover gene mutations that cause childhood brain cancer
Researchers funded by the Canadian Cancer Society have discovered eight similar genes that, when mutated, appear to be responsible for medulloblastoma - the most common of childhood brain cancers. The findings are published today in the online edition of the journal Nature Genetics.
Cancer cells with a long breath: seeking the origin of brain tumors in children
Medulloblastoma is one of the most common and most malignant brain tumours among children and teenagers. These tumours grow very rapidly, and fifty percent of patients in the long term die from the condition.
Childhood brain tumor traced to normal stem cells gone bad
An aggressive childhood brain tumor known as medulloblastoma originates in normal brain "stem" cells that turn malignant when acted on by a known mutant, cancer-causing oncogene, say researchers from Dana-Farber Cancer Institute and the University of California, San Francisco (UCSF).
Certain anticancer agents could be harmful to patients with heart disease
A set of promising new anticancer agents could have unforeseen risks in individuals with heart disease, suggests research at Washington University School of Medicine in St. Louis.
Protein protects embryonic stem cells' versatility and self-renewal
A protein known as REST blocks the expression of a microRNA that prevents embryonic stem cells from reproducing themselves and causes them to differentiate into specific cell types, scientists at The University of Texas M. D. Anderson Cancer Center report in the journal Nature.
St. Jude finds signaling system that halts the growth of a childhood brain cancer
A discovery by St. Jude Children's Research Hospital scientists suggests a safer way to treat medulloblastoma, a rare but often fatal childhood brain tumor. The group found that one of the brain's signaling pathways inhibits the growth of the highly aggressive cancer cells.
St. Jude defines eye cancer gene's role in retinal development
A genetic discovery led by scientists at St. Jude Children's Research Hospital helps answer a long-standing mystery about the eyes of vertebrates, and may translate into a deeper understanding of how genes coordinate the complex process of eye formation and how a rare pediatric eye cancer progresses.
Statin plus cancer drug deliver combo punch to brain cancer cells
Building on newly discovered genetic threads in the rich tapestry of biochemical signals that cause cancer, a Johns Hopkins Kimmel Cancer Center team has dramatically killed brain cancer cells by blocking those signals with a statin and an experimental antitumor drug.
Brain tumor researchers find their 'niche'
Brain tumors appear to arise from cancer stem cells (CSCs) that live within microscopic protective "niches" formed by blood vessels in the brain; and disrupting these niches is a promising strategy for eliminating the tumors and preventing them from re-growing.
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