Telomere maintenance mechanisms are activated in ganglioneuroblastoma and ganglioneuroma

Sugawara,Motoki; Haruta,Masayuki; Ohira,Miki; Akter,Jesmin; Onuki,Ritsuko; Sugino,Ryuichi P.; Ando,Kiyohiro; Nakazawa,Atsuko; Okita,Hajime; Takimoto,Tetsuya; Iehara,Tomoko; Koshinaga,Tsugumichi; Uehara,Shuichiro; Kamijo,Takehiko

doi:10.3892/ol.2026.15509

May-2026 Volume 31 Issue 5

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May-2026 Volume 31 Issue 5

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Article Open Access

Telomere maintenance mechanisms are activated in ganglioneuroblastoma and ganglioneuroma

Authors:
- Motoki Sugawara
- Masayuki Haruta
- Miki Ohira
- Jesmin Akter
- Ritsuko Onuki
- Ryuichi P. Sugino
- Kiyohiro Ando
- Atsuko Nakazawa
- Hajime Okita
- Tetsuya Takimoto
- Tomoko Iehara
- Tsugumichi Koshinaga
- Shuichiro Uehara
- Takehiko Kamijo
View Affiliations / Copyright

Affiliations: Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama 362‑0806, Japan, Department of Clinical Research, Saitama Children's Medical Center, Saitama 330‑8777, Japan, Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo 160‑8582, Japan, Department of Cancer Data Management, National Center for Child Health and Development, Tokyo 157‑8535, Japan, Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602‑8566, Japan, Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173‑8610, Japan

Copyright: © Sugawara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 156
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Published online on: March 4, 2026

https://doi.org/10.3892/ol.2026.15509
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Abstract

Telomere maintenance mechanisms (TMM) have garnered attention as a mechanism associated with the treatment resistance and poor prognosis of neuroblastoma (NB). Ganglioneuroblastoma (GNB) and ganglioneuroma (GN) are histologically classified as neuroblastic tumors (NTs) along with NB; however, few reports have addressed TMM in GNB and GN. The present study analyzed 321 NTs diagnosed in Japan, including 255 NB cases, 48 GNB cases and 18 GN cases, using a quantitative PCR‑based C‑circle assay for alternative lengthening of telomeres (ALT) and a telomerase reverse transcriptase (TERT) mRNA expression assay. ALT was identified in 38 NB cases (38/255, 15%) and 6 GNB cases (6/48, 12.5%), but not in GN. High TERT expression was observed in 38% (64/169), 23% (7/31) and 14% (1/7) of NB, GNB and GN cases, respectively. TMM activation, defined as ALT(+) and/or high TERT expression, occurred in 12/48 GNB cases and 1/18 GN cases, particularly in the GNB‑nodular type (10/21, 48%), which was similar to 39% (100/255) of NB cases. Furthermore, TMM(+) GNBs exhibited distinct features, including a high frequency of ATRX alterations and a lower frequency of TERT rearrangements. Chromosomal aberration analysis revealed frequent 7q gain, 17q gain and 11q loss in ALT(+) NTs (83%). Overall, TMM serves as a poor prognostic marker for high‑risk NB and offers valuable insights for the risk classification of GNBs.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Telomere maintenance mechanisms are activated in ganglioneuroblastoma and ganglioneuroma

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