Cancer Research and Treatment

Original Articles

Central nervous system

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma: Changhee Park, Tae Min Kim, Jeong Mo Bae, Hongseok Yun, Jin Wook Kim, Seung Hong Choi, Soon-Tae Lee, Joo Ho Lee, Sung-Hye Park, Chul-Kee Park; Cancer Res Treat. 2021;53(2):389-398. Published online November 9, 2020; DOI: https://doi.org/10.4143/crt.2020.694

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Purpose
The treatment outcomes and genomic profiles of diffuse midline glioma (DMG) in adult patients are rarely characterized. We performed a retrospective study to evaluate the clinicogenomic profiles of adult patients with brain DMG.
Materials and Methods
Patients aged ≥ 18 years diagnosed with brain DMG at Seoul National University Hospital were included. The clinicopathological parameters, treatment outcomes, survival, and genomic profiles using 82-gene targeted next-generation sequencing (NGS) were analyzed. The 6-month progression-free survival (PFS6) after radiotherapy and overall survival (OS) were evaluated.
Results
Thirty-three patients with H3-mutant brain DMG were identified. The median OS from diagnosis was 21.8 months (95% confidence interval [CI], 13.2 to not available [NA]) and involvement of the ponto-medullary area tended to have poor OS (median OS, 20.4 months [95% CI, 9.3 to NA] vs. 43.6 months [95% CI, 18.2 to NA]; p=0.07). Twenty-four patients (72.7%) received radiotherapy with or without temozolomide. The PFS6 rate was 83.3% (n=20). Patients without progression at 6 months showed significantly prolonged OS compared with those with progression at 6 months (median OS, 24.9 months [95% CI, 20.4 to NA] vs. 10.8 months [95% CI, 4.0 to NA]; p=0.02, respectively). Targeted NGS was performed in 13 patients with DMG, among whom nine (69.2%) harbored concurrent TP53 mutation. Two patients (DMG14 and DMG23) with PIK3CA^R38S+E545K and KRAS^G12A mutations received matched therapies. Patient DMG14 received sirolimus with a PFS of 8.4 months.
Conclusion
PFS6 after radiotherapy was associated with prolonged survival in adult patients with DMG. Genome-based matched therapy may be an encouraging approach for progressive adult patients with DMG.

Citations

Citations to this article as recorded by

Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients
Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon
Cancer Research and Treatment.2025; 57(2): 378. CrossRef
The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study
Vincenzo Di Nunno, Giuseppe Lombardi, Matteo Simonelli, Giuseppe Minniti, Angela Mastronuzzi, Valentina Di Ruscio, Martina Corrà, Marta Padovan, Marta Maccari, Mario Caccese, Giorgia Simonetti, Arianna Berlendis, Mariangela Farinotti, Bianca Pollo, Manila
Journal of Neuro-Oncology.2024; 167(1): 145. CrossRef
Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort
Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano
Acta Neuropathologica Communications.2024;[Epub] CrossRef
Genetic alteration analysis of non-pediatric diffuse midline glioma, H3 K27-altered
Hanbin Jang, Seyoung Moon, Hyun Jung Kwon, Sejoon Lee, Gheeyoung Choe, Kyu Sang Lee
Human Pathology.2024; 154: 105709. CrossRef
How to treat histone 3 altered gliomas: molecular landscape and therapeutic developments
Vincenzo Di Nunno, Enrico Franceschi, Lidia Gatto, Alicia Tosoni, Stefania Bartolini, Alba Ariela Brandes
Expert Review of Clinical Pharmacology.2023; 16(1): 17. CrossRef
Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis
Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, Sung-Hye Park
Scientific Reports.2023;[Epub] CrossRef
Radiotherapy and radio‐sensitization in H3K27M‐mutated diffuse midline gliomas
Chao Liu, Shuwen Kuang, Lei Wu, Quan Cheng, Xuan Gong, Jun Wu, Longbo Zhang
CNS Neuroscience & Therapeutics.2023; 29(7): 1721. CrossRef
Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy
A. Knight, P. Horsley, A. Yuile, J. Yim, M. Suh, V. Venketesha, M. Kastelan, H. Wheeler, M. Back
Journal of Neuro-Oncology.2023; 163(1): 281. CrossRef
Differences in survival prognosticators between children and adults with H3K27M‐mutant diffuse midline glioma
Xuan Gong, Shuwen Kuang, Dongfeng Deng, Jun Wu, Longbo Zhang, Chao Liu
CNS Neuroscience & Therapeutics.2023; 29(12): 3863. CrossRef
Adult spinal cord diffuse midline glioma, H3 K27-altered mimics symptoms of central nervous system infection: a case report
Xue Chen, Yi Li, Hui Bu, YueLi Zou, JunYing He, Hu Liu
Frontiers in Neurology.2023;[Epub] CrossRef
Clinicogenetic characteristics and the effect of radiation on the neural stem cell niche in subventricular zone-contacting glioblastoma
Jee Ye Kahng, Byung-Hee Kang, Soon-Tae Lee, Seung Hong Choi, Tae Min Kim, Chul-Kee Park, Jae-Kyung Won, Sung-Hye Park, Jaeman Son, Joo Ho Lee
Radiotherapy and Oncology.2023; 186: 109800. CrossRef
H3 K27M-Altered Diffuse Midline Gliomas: A Review
Karol Wiśniewski, Andrew Ghaly, Kate Drummond, Andreas Fahlstrӧm
Indian Journal of Neurosurgery.2023; 12(02): 104. CrossRef
Adult diffuse midline gliomas H3 K27-altered: review of a redefined entity
Carlos Axel López-Pérez, Xochitl Franco-Mojica, Ricardo Villanueva-Gaona, Alexandra Díaz-Alba, Marco Antonio Rodríguez-Florido, Victor Garcia Navarro
Journal of Neuro-Oncology.2022; 158(3): 369. CrossRef
H3K27M-Altered Diffuse Midline Gliomas Among Adult Patients: A Systematic Review of Clinical Features and Survival Analysis
Othman Bin-Alamer, Adrian E. Jimenez, Tej D. Azad, Chetan Bettegowda, Debraj Mukherjee
World Neurosurgery.2022; 165: e251. CrossRef
Molecular profile and clinical features of patients with gliomas using a broad targeted next generation‑sequencing panel
Ourania Romanidou, Paraskevi Apostolou, Kyriakos Kouvelakis, Kyriakos Tsangaras, Alexia Eliades, Achilleas Achilleos, Charalambos Loizides, Christos Lemesios, Marios Ioannides, Elena Kypri, George Koumbaris, Kyriaki Papadopoulou, Athanasios Papathanasiou,
Oncology Letters.2022;[Epub] CrossRef

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16 Web of Science
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Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma: Young-Bem Se, Seung Hyun Kim, Ji Young Kim, Ja Eun Kim, Yun-Sik Dho, Jin Wook Kim, Yong Hwy Kim, Hyun Goo Woo, Se-Hyuk Kim, Shin-Hyuk Kang, Hak Jae Kim, Tae Min Kim, Soon-Tae Lee, Seung Hong Choi, Sung-Hye Park, Il Han Kim, Dong Gyu Kim, Chul-Kee Park; Cancer Res Treat. 2017;49(2):387-398. Published online July 19, 2016; DOI: https://doi.org/10.4143/crt.2016.106

Abstract PDF Supplementary Material PubReader ePub

Purpose
Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance.
Materials and Methods
The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis.
Results
The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith lowHOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified.
Conclusion
The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

Citations

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