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Novel method that identifies mutations in childhood brain tumors
Overview
Researchers at Uppsala University have developed a new method to find mutations in brain tumors in children. They could also show that the mutations identified by them change how cancer cells respond to a cancer drug. These findings could lead to better diagnostics and more individualized treatment of children with brain tumors. The study is published in the journal PNAS.
To gain a comprehensive view of what mutations are important in medulloblastoma, the researchers used a method that they recently developed as part of an international consortium. The method specifically looks at conserved positions in the genome and builds on the assumption that DNA sequences that have remained the same over millions of years of evolution are likely to have important functions.
Of the 200 000 mutations found in 145 patients, a total of 114 mutations were found in conserved positions in the genome. Many of these mutations occurred in genes that were previously not reported to be mutated in this cancer, even though some of the genes had altered protein levels in medulloblastoma. The newly identified mutations are located in DNA that contains instructions about where, when and how much proteins should be made. The results may therefore explain earlier observations of different protein levels in medulloblastoma.
The researchers found different mutations in different age groups and different subgroups of medulloblastoma, and that the mutations changed gene expression in medulloblastoma cells in culture.
Reference: Using evolutionary constraint to define novel candidate driver genes in medulloblastoma, Proceedings of the National Academy of Sciences, DOI 10.1073/pnas.2300984120
Speakers
Isra Zaman
B.Sc Life Sciences, M.Sc Biotechnology, B.Ed