Pediatric Oncology: Looking for Similarities Between the Mechanisms Leading to Acute Lymphoblastic Leukemia and Neuroblastoma

Abstract

Most adult cancer is caused by acquiring mutations over time, but much less is known about the causes of childhood cancers. neuroblastoma and acute lymphoblastic leukemia are amongst the most common pediatric cancers. Both have a subgroup that present with very similar characteristics, which could indicate that they might share a mechanistic origin. In contrast, the High Risk subgroup of neuroblastoma has a poor outcome and is much different from Low Risk neuroblastoma. In this review, what is known about the mechanisms of these two types of pediatric cancer have been compared to find similarities and differences. These can help researchers to formulate new hypotheses to better study pediatric cancer. A mechanism these tumors might share is an error in cell division, causing the chromosomes to be incorrectly segregated. This results in number of chromosomes per cell deviating from the normal 46. However, it also seems likely that neuroblastoma (NB) is caused by whole genome duplication and subsequently loses chromosomes. The High Risk subgroup of neuroblastoma is driven by amplification of the oncogene MYCN. MYCN causes activation of telomerase, which causes telomere maintenance. Telomere maintenance is required to prevent the loss of DNA at the chromosome ends. It is unclear what causes MYCN amplification and it has been proposed that this is due to the shortening of telomeres, which causes chromosome fusion resulting in complex DNA damage