Chapters authored
Telomeres and Telomerase in Neuroblastoma
Telomeres are nucleoprotein structures located at the ends of linear chromosomes. In most human adult normal somatic cells, telomeres shorten after each cellular division. This shortening ultimately leads to senescence and/or apoptosis. By contrast, in most cancer cells, telomerase activation compensates this loss and confers to these cells their infinite cell proliferation potential. Neuroblastoma (NBL) is a malignant tumor of the peripheral sympathetic nervous system and the most frequent extracranial solid tumor of childhood. NBLs are remarkably heterogeneous both at the levels of biology, genetic and clinical courses. Indeed, some of NBLs can regress spontaneously or after a mild treatment, while others are in the high-risk category with poor prognosis. The molecular bases underlying this heterogeneity are poorly understood. MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-derived Homolog) amplification, recognized as strongly associated with unfavorable patient outcome, is found in only 40% of the high-risk disease, indicating the involvement of other mechanisms. Recent observations suggest that telomerase expression and telomere dysfunctions may be one critical step in NBL development. This review provides recent insights on telomeres/telomerase regulation in NBL. Because of their involvement in the tumor cell biology, telomere and telomerase are currently at the core of new drug development.
Part of the book: Neuroblastoma