Telomere Maintenance in Pediatric Cancer

Abstract

Telomere length has been proposed as a biomarker of biological age and a risk factor for age-related diseases and cancer. Substantial progress has been made in recent decades in understanding the complex molecular relationships in this research field. However, the majority of telomere studies have been conducted in adults. The data on telomere dynamics in pediatric cancers is limited, and interpretation can be challenging, especially in cases where results are contrasting to those in adult entities. This review describes recent advances in the molecular characterization of structure and function of telomeres, regulation of telomerase activity in cancer pathogenesis in general, and highlights the key advances that have expanded our views on telomere biology in pediatric cancer, with special emphasis on the central role of telomere maintenance in neuroblastoma. Furthermore, open questions in the field of telomere maintenance research are discussed in the context of recently published literature.

Genetic changes associated with relapse in favorable histology Wilms tumor: A Children’s Oncology Group AREN03B2 study

“…Telomerase maintains telomere length, thereby maintaining self-renewal potential. Somatic mutations in the promoter of TERT , the catalytic subunit of telomerase, have been reported in several tumor types and are predicted to increase promoter activity and TERT transcription 2- to 6-fold (reviewed by Ackerman and Fischer 50 ). These promoter mutations were associated with high expression of TERT in the current study ( Figure 2 ).…”

Nucleolin expression has prognostic value in neuroblastoma patients

“…Along with MYCN , also TERT and MYC are well-known genes whose deregulation has been associated with unfavourable NB patient prognosis. 41 , 42 The expression of NCL , which is a target gene of both MYCN and MYC , 43 , 44 positively correlates with MYCN expression and negatively correlates with MYC expression. These results seem to be in agreement with the inverse correlation of MYCN and MYC expression in NB subtypes.…”

Biological Aging and Immune Senescence in Children with Perinatally Acquired HIV

“…They displayed significantly shorter telomere length compared to age-matched healthy controls; they also showed a mild association with lower IQ. Childhood cancers sometimes need to be addressed differently from adult ones; one of the reasons resides in the differences in the mutational landscapes and the prevalence of telomere maintenance mechanisms [175]. Environmental and behavioral factors might also impact on telomere length and erosion in newborns, children, and adolescents.…”