Medulloblastoma is a rare malignant tumor of the cerebellum and occurs predominantly in children. Scientists believe that in many cases hereditary gene defects trigger the development of this malignant disease. However, there are no standards for routine genetic screening of patients, nor are there guidelines and a corresponding nationwide infrastructure for genetic counseling of affected families.

Scientists have now been able to characterize medulloblastoma more accurately and to derive recommendations for genetic testing based on analysis of 1,022 patients with medulloblastoma. "We analyzed genes that have been previously implicated in predisposition to any type of pediatric and adult cancer," says Sebastian Waszak from the EMBL Heidelberg who is one of the study's lead authors. It turned out that six genes were also frequently affected by genetic alterations in patients with medulloblastoma.

Considering the six significantly enriched genes, about 5% of patients had an increased risk of cancer. Taking into account all cancer risk genes, about 11% of the patients had an increased cancer risk. Looking at a particular tumor subgroup, the so called "SHH-activated medulloblastoma," even 20% were identified to harbor a genetic predisposition to cancer.

These predisposing mutations occur in every single cell of the patient and can be also passed on to offspring. "Mutations of this kind often indicate a familial predisposition to cancer and therefore place special demands on the treatment of patients and the counseling of families," said Paul Northcott from the St. Jude Children's Research Hospital in Memphis, who shares the lead authorship. The results are particularly important because both materials from previous studies and patient data from four current or recently completed clinical trials were included in the analysis.

Based on these findings and other tumor features, the scientists developed criteria for routine genetic screening. "Hereditary disease factors usually have a significant impact on the whole family of the patient. We want to make genetic analysis available as a standard-of-care for patients with specific medulloblastoma," says Stefan Pfister, KiTZ director, scientist at the German Cancer Research Center, and senior physician at the Heidelberg University Hospital. To make this possible, Stefan Pfister and Christian Kratz from the Hannover Medical School have created a registry for patients with a hereditary cancer predisposition and a web site that contains information for patients, families, and physicians (www.krebs-praedisposition.de).