Neuroblastomas (NB) are one of the most common extracranial solid tumors in children, and they frequently display high heterogeneity in the disease course. With ongoing research, more information regarding the genetic etiology and molecular mechanisms underlying these contrasting phenotypes is being uncovered. The proto-oncogene MYCN is amplified in approximately 20% of NB cases and is considered a indicator of poor prognosis and an indicator of high-risk NB. The poor prognosis of high risk NB is incompletely explained by MYCN amplification. Recently, massive parallel sequencing studies reported several relatively common gene alterations, such as ATRX mutation and TERT rearrangement that are involved in telomere maintenance through telomerase activity and alternative lengthening of telomeres. Thus, these are important for understanding the etiology and molecular pathogenesis of NB, and hence, for identifying diagnostic and treatment markers. Development of telomerase inhibitors and identification of alternative lengthening of telomeres related targets will contribute to the individualized treatment for high-risk NB. In this mini-review, we will discuss the research progress of TERT-mediated and ATRX-mediated telomere maintenance and NB, especially high-risk tumors.
Journal of Pediatric Hematology / Oncology – Wolters Kluwer Health
Published: Jan 1, 2018
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