Scientists at the Johns Hopkins Kimmel Cancer Center has decoded genetically Medulloblastoma, the most common pediatric brain cancer and leading killer of children with cancer. The results show that children with medulloblastoma have five- to tenfold fewer cancer-linked alterations in their genomes compared with their adult counterparts. The scientists team used automated tools to sequence hundreds of millions of individual chemicals called nucleotides, which pair together in a preprogrammed fashion to build DNA and, in turn, a genome. Combinations of these nucleotide letters form genes, which provide instructions that guide cell activity. Alterations in the nucleotides, called mutations, can create coding errors that transform a normal cell into a cancerous one. For the study, scientists sequenced nearly all protein-encoding genes in 22 samples of pediatric medulloblastoma and compared these sequences with normal DNA from each patient to identify tumor-specific changes or mutations. Each tumor sample had an average of 11 mutations. There were 225 mutations in all.Then, the investigators searched through a second set of 66 medulloblastomas, including some samples from adults, to find how these mutations altered the proteins made by the genes.The scientists found that most of the mutations stay within a few gene families or pathways. The most common pathway ordered the way long strands of DNA, that make up chromosomes, are twisted and shaped into dense packets that open and close depending on when genes need to be activated. Such a process is regulated by chemicals that operate outside of genes, termed “epigenetic” by scientists. Within the epigenetic pathway, two commonly mutated genes were both involved in how molecules called histones wrap around DNA.
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