Speaker: Marcel Kool
Department: Division of pediatric neuro-oncology, DKFZ Heidelberg
Subject: Molecular classification of pediatric brain tumors reveals new entities
Location: JWI-Oncology, Erasmus MC Rotterdam
Author: Mirte Golverdingen
A very important part of finding a cure to cancer is to know which medicine you need to use. Marcel Kool is a researcher of the division of pediatric neuro-oncology in Heidelberg. He is currently working on the classification of brain tumors. If you know which tumor causes the cancer, you can find more easily a treatment for this tumor.
There are a lot of different brain tumors, and almost all have different treatments. Tumors are graded in a grading system with four levels, if the grading is higher, the tumor will be more aggressive and harder to treat. Moreover, tumors are classified in different groups by looking at the morphology and the way they develop. Research gives that this classification is not complete, there are more and/or different subgroups that not yet have been revealed.
The DKFZ in Heidelberg uses DNA methylation to classify brain tumors, this is a very robust technique that is very useful for molecular profiling of tumors. They found first of all 2 new subgroups in the Glioblastoma group. This research resulted in new target therapies for patients.
Moreover, their research revealed that there are not 2 but 9 subgroups in Ependymal tumors. In these group there was no distinction between grade II and grade III. This resulted in the conclusion that the current grades of tumors are not accurate. A very interesting result because patients are currently treaded by their grades.
The research group also concluded that there are 3 subgroups in the ATRT group. However, the most special result of this group is that the CNS-PNET group doesn’t exist. It was considered as a grade IV heterogeneous tumor group and hard to treat. The research gives that 70% of the sub-groups can be reclassified in known entities. The remaining subgroups form 4 new groups that all have specific processes that drive the forming of the tumor. Above that unclassified tumors could be classified in this new groups. It results in better and more specific treatments than before.
I did know that tumors where classified in different groups, but I didn’t realize that it was so important for the treatment of the tumors. This research results in better and more effective treatments for patients. The lecture was a good insight into the current research of cancer, and how important DNA research is in this process. The plans of the research group to start algorithms to classify brain tumors and start a database are very exciting. This is a good way to share the knowledge they gain at the lab.
Figure 1: Microscopical appearance (a, d, g), FISH analysis of the 19q13.42 locus (b, e, h), LIN28A immunohistochemistry (c, f, i) of ETANTR (a–c), EBL (d–f) and MEPL (g–i). Amplification of 19q13.42 (b, e, h) and LIN28A immunoexpression (c, f, i) was detected in all three histological ETMR subtypes. For the FISH analysis the C19MC 19q13.42 probe (green signals) and a reference 19p13 probe were used (red signals) (Source: Korshunov A, Sturm D, Ryzhova M, et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. Acta Neuropathologica. 2014;128(2):279-289. doi:10.1007/s00401-013-1228-0)