In two patients with the same disease within a tumor may be different. In one patient, the cancer progresses rapidly, while other tumor grows slowly. Therapy can reduce it or do not have any effect. Some patients survive, while others - not. Profiling of tumors at the DNA, RNA or epigenetic levels identified subtypes of tumors that help oncologists diagnose and predict cancer, but still unclear as to convert these data into new molecular therapeutic agents.
Looking beyond the genome and analyzed the tumor proteins, scientists have identified a previously unknown subtypes of medulloblastoma. Scientists at the Massachusetts Institute of Technology, Harvard University and Children's Hospital Boston have combined clinical, technical and bioinformatics knowledge, to show that the multi-purpose approach, aimed not only at the genetic material, but also on proteins and their modifications will help to discover new biomarkers or drug targets.
The researchers published the results in Cancer Cell. They also created a set of data and share them with the scientific community.
To systematically examine the protein modification during medulloblastoma, researchers have collected 45 tumor samples analyzed tumors and proteins that can be modified in the cell. Then, the data were integrated with measurements of DNA and RNA, in collaboration with the German Cancer Research Center.
"In the field of proteomic technologies Recent developments, especially with regard to the analysis of the modifications have allowed us to carry out one of the most comprehensive proteomic research medulloblastoma today, giving a deeper understanding of this disease," - the researchers explain.
Although only a few dozen samples were tested, the results include the hundreds of thousands of different measurements. This comprehensive data set was analyzed by a team of computational biologists. The four existing medulloblastoma subgroups, researchers found new subtypes. Adding data about proteins and their modifications allowed us to see the differences in the subgroups of medulloblastoma tumors that can not be seen in the analysis of RNA. The data showed that the tumor 3 group can be divided into two subtypes, with one sub-type, which is caused by mutations associated with the MYC oncogene, has a very poor prognosis.
To interpret the data, the researchers developed a new approach to the forecasting of key regulatory proteins, which caused the changes observed in proteomic data. For example, scientists have found protein PRKDC, which makes one subtype tumors more sensitive to radiotherapy.
"Patients with medulloblastoma need better methods of treatment, - the researchers say. - We hope that these findings will lead to new therapeutic strategies and fewer long-term side effects. "