Telomeres and Telomerase in Neuroblastoma

Abstract

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.

hMZF-2, the Elusive Transcription Factor

“…Herein, we summarize the available information regarding MZF-2 published as original research articles (Murai et al, 1997(Murai et al, , 1998Fujimoto et al, 2000) and those published in review articles (Ducrest et al, 2002;Pericuesta et al, 2006;Jafri et al, 2016;Lewis and Tollefsbol, 2016;ElHajj et al, 2017;Heidenreich and Kumar, 2017;Eitsuka et al, 2018;Srinivas et al, 2020). All the published reports, as well as the search in genomic databases, lead us to be doubtful about the real existence of the human form hMZF-2.…”

“…this initial report, these four binding sites were presented in several figures of book chapters or review articles on telomerase regulation, including recently published ones (Ducrest et al, 2002;Pericuesta et al, 2006;Jafri et al, 2016;Lewis and Tollefsbol, 2016;ElHajj et al, 2017;Heidenreich and Kumar, 2017;Eitsuka et al, 2018;Srinivas et al, 2020), without any additional report that stated unambiguously the existence of hMZF-2 while the presence of other regulators of the hTERT gene, located further upstream of the transcription start site (TSS), were clearly reported to influence the hTERT expression, such as the activator protein 1 (AP-1), vitamin D (3) receptor (VDR), signal transducer and activator of transcription 3 (STAT3), and nuclear factor κB (NF-κB) (Ramlee et al, 2016).…”

Long telomeres cooperate with p53,MDM2, and p21 polymorphisms to raise pediatric solid tumor risk

“…Therefore, pediatric tumorigenesis must involve longer telomeres in order to bypass p53‐mediated cellular senescence and achieve immortalization. In epidemiological studies longer telomeres have been associated with elevated risk for certain tumors, but relatively shorter telomeres have also been reported to be associated with increased risk, poor prognosis and malignant secondary neoplasms in children . Taken together, these data suggest a potentially significant role of telomeres in the prediction of childhood cancer risk, but the association remains unclear.…”