Inherited Mutation Can Predispose Children to Medulloblastoma

Researchers at St. Jude Children’s Research Hospital, the European Molecular Biology Laboratory, and the German Cancer Research Center have identified a novel predisposition gene, ELP1, in the subgroup of a common pediatric brain tumor, medulloblastoma, according to a study published in Nature.

The team looked at all protein-coding genes (the exome) in more than 1,000 patients with medulloblastoma. The researchers compared their medulloblastoma findings to more than 118,000 exomes from several databases of individuals without cancer. According to the results, ELP1 is abnormally mutated in the germline DNA of 14-15% of children with SHH medulloblastoma.

Moreover, with the addition of ELP1 to the list of known cancer predisposition genes, the researchers showed that at least 40% of pediatric SHH medulloblastoma is driven by an inherited abnormality. ELP1 mutations occur at more than double the rate of any other previously acknowledged cancer predisposition gene in SHH medulloblastoma.

“When multiple members of a family have the same kind of medulloblastoma, but don’t have mutations in any of the recognizable predisposition genes, there has to be more to the story,” said co-first author Giles Robinson, M.D., of the St. Jude Department of Oncology in a press release. “ELP1 has not been part of routine genetic testing offered to patients and families, but this work suggests that it should be included for medulloblastoma.”