Researchers have pinpointed a crucial change in a single DNA base that both predisposes children to an aggressive form of the childhood cancer neuroblastoma and makes the disease progress once tumors form.
The change in the LMO1 gene results in a "super-enhancer," driving abnormally increased biological activity in the gene, resulting in tumor formation and progression. The study was published in the journal in Nature.
A cancer of the peripheral nervous system that usually occurs as a solid tumor in a child's chest or abdomen, neuroblastoma is the most common cancer in infants. It accounts for a disproportionate share of cancer deaths in children.
By mapping how DNA interacts with regulatory proteins that control transcription, the researchers narrowed down the culprit to the location where a single DNA base, guanine, drives super-enhancer activity, boosting LMO1 gene expression and causing tumors to arise and grow out of control.
The researchers also found that another genetic change has a beneficial effect: if the DNA base at the specified location is a different letter of the genetic alphabet, thymine instead of guanine, it protects against neuroblastoma. Gene studies in human populations suggest that this protective gene variant evolved after human ancestors migrated out of Africa, hundreds of thousands of years ago.