Masumi Kawashima1, Masato Kojima1, Yuka Ueda1, Sho Kurihara1, Eiso Hiyama2. 1. Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan; Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan. 2. Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan; Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan; Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University, Hiroshima, Japan. Electronic address: eiso@hiroshima-u.ac.jp.
Abstract
PURPOSE: Our telomere biology study of neuroblastomas (NBLs) has revealed that unfavorable NBLs acquired telomere stabilization by telomerase activation or ALT (alternative lengthening of telomeres). Recently, genomic rearrangements in a region proximal to the telomerase reverse transcriptase (TERT) gene have been discovered in NBLs. In this study, TERT rearrangements were examined in NBLs along with their relationship to other aspects of telomere biology. METHODS: In 121 NBLs, including 67 cases detected by mass-screening whose telomere length, telomerase activity, ALT with ATRX/DAXX alterations, and MYCN amplification were already known, TERT rearrangements were examined using GeneChip SNP arrays. RESULTS: The 11 ATRX/DAXX mutated ALT cases and 29 cases with high telomerase activity showed poor prognosis. MYCN amplification and TERT rearrangements were independently detected in 16 and 13 cases, respectively, and these alterations were significantly correlated with high telomerase activity. In 81 infant cases, MYCN amplification, TERT rearrangements and ATRX mutations were detected in 3, 4, and 3 cases, respectively. Among them, 6 cases showed progression or recurrences. CONCLUSIONS: Telomere stabilization in NBLs is acquired by telomerase activation through MYCN amplification, TERT rearrangements or by ALT. Since these tumors usually show progression and recurrence, complete resection should be considered, even in infant cases. LEVEL OF EVIDENCE: Prognosis study, level III. Copyright Â
PURPOSE: Our telomere biology study of neuroblastomas (NBLs) has revealed that unfavorable NBLs acquired telomere stabilization by telomerase activation or ALT (alternative lengthening of telomeres). Recently, genomic rearrangements in a region proximal to the telomerase reverse transcriptase (TERT) gene have been discovered in NBLs. In this study, TERT rearrangements were examined in NBLs along with their relationship to other aspects of telomere biology. METHODS: In 121 NBLs, including 67 cases detected by mass-screening whose telomere length, telomerase activity, ALT with ATRX/DAXX alterations, and MYCN amplification were already known, TERT rearrangements were examined using GeneChip SNP arrays. RESULTS: The 11 ATRX/DAXX mutated ALT cases and 29 cases with high telomerase activity showed poor prognosis. MYCN amplification and TERT rearrangements were independently detected in 16 and 13 cases, respectively, and these alterations were significantly correlated with high telomerase activity. In 81 infant cases, MYCN amplification, TERT rearrangements and ATRX mutations were detected in 3, 4, and 3 cases, respectively. Among them, 6 cases showed progression or recurrences. CONCLUSIONS: Telomere stabilization in NBLs is acquired by telomerase activation through MYCN amplification, TERT rearrangements or by ALT. Since these tumors usually show progression and recurrence, complete resection should be considered, even in infant cases. LEVEL OF EVIDENCE: Prognosis study, level III. Copyright Â
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