Review
Biochemistry & Molecular Biology
Alexander Yuile, Laveniya Satgunaseelan, Joe Wei, Marina Kastelan, Michael F. Back, Maggie Lee, Heng Wei, Michael E. Buckland, Adrian Lee, Helen R. Wheeler
Summary: Mutations in both IDH1 and IDH2 play an important role in the development of gliomas, but the co-occurrence of IDH1 and IDH2 mutations in the same tumor is rare. This study describes a case of an IDH-mutant astrocytoma with both IDH1 and IDH2 mutations, and the patient remains disease-free after nine and a half years. Interrogation of cancer genomic databases and a systematic review confirm the rarity of the concurrent mutations.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Clinical Neurology
C. Mircea S. Tesileanu, Wies R. Vallentgoed, Marc Sanson, Walter Taal, Paul M. Clement, Wolfgang Wick, Alba Ariela Brandes, Jean Francais Baurain, Olivier L. Chinot, Helen Wheeler, Sanjeev Gill, Matthew Griffin, Leland Rogers, Roberta Ruda, Michael Weller, Catherine McBain, Jaap Reijneveld, Roelien H. Enting, Francesca Caparrotti, Thierry Lesimple, Susan Clenton, Anja Gijtenbeek, Elizabeth Lim, Filip de Vos, Paul J. Mulholland, Martin J. B. Taphoorn, Iris de Heer, Youri Hoogstrate, Maurice de Wit, Lorenzo Boggiani, Sanne Venneker, Jan Oosting, Judith V. M. G. Bovee, Sara Erridge, Michael A. Vogelbaum, Anna K. Nowak, Warren P. Mason, Johan M. Kros, Pieter Wesseling, Ken Aldape, Robert B. Jenkins, Hendrikus J. Dubbink, Brigitta Baumert, Vassilis Golfinopoulos, Thierry Gorlia, Martin van den Bent, Pim J. French
Summary: Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are common in various tumor types, with gliomas showing a particularly high frequency of the IDH1(R132H) mutation. Patients with IDH1(R132H) mutations tend to have lower DNA methylation levels and higher gene expression compared to other IDH1/2 mutations. The different prognosis between IDH1(R132H) mutated astrocytomas and non-R132H IDH1/2-mutated astrocytomas highlights the clinical relevance of distinct IDH mutations.
ACTA NEUROPATHOLOGICA
(2021)
Article
Oncology
Mathieu Simonin, Aline Schmidt, Christophe Bontoux, Marie-Emilie Dourthe, Etienne Lengline, Guillaume P. Andrieu, Ludovic Lhermitte, Carlos Graux, Nathalie Grardel, Jean-Michel Cayuela, Francoise Huguet, Isabelle Arnoux, Stephane Ducassou, Elizabeth Macintyre, Virginie Gandemer, Herve Dombret, Arnaud Petit, Norbert Ifrah, Andre Baruchel, Nicolas Boissel, Vahid Asnafi
Summary: IDH2 mutations in T-ALL are associated with older age, an immature phenotype, more frequent RAS gain-of-function mutations, and epigenetic regulator loss-of-function alterations. Conversely, IDH1 mutations appeared to be an independent prognostic factor in multivariate analysis.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Medicine, General & Internal
Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit Yust-Katz, Liam Welsh, Warren P. Mason, Francois Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan M. Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, Timothy F. Cloughesy
Summary: In a phase 3 trial, vorasidenib showed significant improvement in progression-free survival and delay in the time to the next intervention for patients with grade 2 IDH-mutant glioma.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Oncology
Gabrielle W. Johnson, Rowland H. Han, Matthew D. Smyth, Eric C. Leuthardt, Albert H. Kim
Summary: LITT is an effective treatment option for patients with IDH1/2 mutant glioma, as suggested by the outcomes of this study.
Article
Genetics & Heredity
Laila C. Schenkel, Joseph Mathew, Hal Hirte, John Provias, Guillaume Pare, Michael Chong, Daria Grafodatskaya, Elizabeth McCready
Summary: This study aimed to assess the feasibility of DNA methylation array for simultaneous detection of glioma biomarkers. The research found that a DNA methylation signature could specifically distinguish IDH1/IDH2 mutant tumors, and copy number analysis using the array could identify 1p19q co-deletion tumors.
Article
Medical Laboratory Technology
A. K. Murugan, A. S. Alzahrani
Summary: This study analyzed the mutation frequency of IDH1 and IDH2 genes in various cancers and found that they are most commonly mutated in gliomas. The mutations in these genes are associated with better overall survival and progression-free survival in gliomas.
BRITISH JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Clinical Neurology
Ryan M. McCormack, Ping Zhu, Antonio Dono, Takeshi Takayasu, Ankush Bhatia, Angel Blanco, Nitin Tandon, Quinn T. Ostrom, Alberto Gonzales, Sergio Moreno, Leomar Y. Ballester, Yoshua Esquenazi
Summary: The prevalence of IDH2 mutations is higher in Mexican Hispanic individuals compared to US individuals, contributing to the previously reported survival benefit of Hispanic patients. Post-progression survival is significantly shorter in patients from Mexico compared to the US, while overall survival remains similar.
WORLD NEUROSURGERY
(2021)
Article
Medicine, Research & Experimental
Uiju Cho, Seung Ho Yang, Changyoung Yoo
Summary: Most diffuse gliomas are reported to have IDH mutations, although in clinical practice, results are often negative. This study found that IDH1 mutations had different frequencies in different types of gliomas, while IDH2 mutations were relatively rare. Patients with IDH1/2-wildtype anaplastic astrocytomas had poor prognosis similar to glioblastomas.
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
(2021)
Article
Oncology
Monica Niger, Federico Nichetti, Andrea Casadei-Gardini, Mario Domenico Rizzato, Chiara Pircher, Marta Bini, Andrea Franza, Margherita Rimini, Valentina Burgio, Caterina Sposetti, Lorenzo Fornaro, Ilario Giovanni Rapposelli, Francesco Enrico D'Amico, Giuseppe Aprile, Caterina Vivaldi, Giovanni Luca Frassineti, Massimo Milione, Giuseppe Leoncini, Alessandro Cappetta, Enrico Vasile, Matteo Fassan, Federica Morano, Federica Perrone, Elena Tamborini, Giancarlo Pruneri, Sara Lonardi, Vincenzo Mazzaferro, Filippo Pietrantonio, Maria Di Bartolomeo, Filippo de Braud
Summary: This study investigated the impact of IDH1/2 mutations on progression-free survival, overall response rate, and disease control rate in iCCA patients treated with platinum-based chemotherapy. The results showed that IDH1/2 mutations are not associated with increased sensitivity to platinum-based chemotherapy in iCCA patients. Furthermore, the analysis of TCGA data indicated that IDH1/2 mutated CCA did not show higher HRD compared to wild-type cases.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Medicine, General & Internal
Enrico Franceschi, Dario De Biase, Vincenzo Di Nunno, Annalisa Pession, Alicia Tosoni, Lidia Gatto, Giovanni Tallini, Michela Visani, Raffaele Lodi, Stefania Bartolini, Alba Ariela Brandes
Summary: This study found that non-canonical IDH1 mutations may be associated with improved survival among patients with IDH1 mutated grade II-III glioma. These patients were typically younger and less likely to have 1p19q codeletion.
Article
Biochemistry & Molecular Biology
Ingo K. Mellinghoff, Min Lu, Patrick Y. Wen, Jennie W. Taylor, Elizabeth A. Maher, Isabel Arrillaga-Romany, Katherine B. Peters, Benjamin M. Ellingson, Marc K. Rosenblum, Saewon Chun, Kha Le, Ania Tassinari, Sung Choe, Youssef Toubouti, Steven Schoenfeld, Shuchi S. Pandya, Islam Hassan, Lori Steelman, Jennifer L. Clarke, Timothy F. Cloughesy
Summary: In a pilot perioperative randomized clinical trial, the dual IDH1/IDH2 inhibitor vorasidenib was found to have better brain permeability and target engagement than ivosidenib in patients with IDH1-mutant glioma. Both agents showed significant reduction in tumor 2-HG concentrations, with vorasidenib demonstrating more consistent suppression. Exploratory analyses revealed additional positive effects of 2-HG reduction. Vorasidenib was selected for further testing in phase 3 trials. This study was funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC.
Article
Oncology
Joseph P. Eder, Deborah B. Doroshow, Khanh T. Do, Vicki L. Keedy, Jeffrey S. Sklar, Peter Glazer, Ranjit Bindra, Geoffrey Shapiro
Summary: The Olaparib Combination trial showed preliminary activity of PARP inhibitors in patients with IDH1/2-mutant chondrosarcoma and pulmonary epithelioid hemangioendothelioma. Nevertheless, no significant clinical benefit was observed in patients with cholangiocarcinoma.
JCO PRECISION ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Mahmoud A. Bassal, Saumya E. Samaraweera, Kelly Lim, Brooks A. Bernard, Sheree Bailey, Satinder Kaur, Paul Leo, John Toubia, Chloe Thompson-Peach, Tran Nguyen, Kyaw Ze Ya Maung, Debora A. Casolari, Diana G. Iarossi, Ilaria S. Pagani, Jason Powell, Stuart Pitson, Siria Natera, Ute Roessner, Ian D. Lewis, Anna L. Brown, Daniel G. Tenen, Nirmal Robinson, David M. Ross, Ravindra Majeti, Thomas J. Gonda, Daniel Thomas, Richard J. D'Andrea
Summary: This study reveals the mutual exclusivity between germline mutations in mitochondrial complex I and somatic mutations in the metabolic enzyme IDH1 in patients with acute myeloid leukemia (AML), and finds that IDH1 mutant cells have increased sensitivity to complex I inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
M. Saikiran Reddy, Debanjan Bhattacharjee, Nishant Jain
Summary: The study reveals that the mitotic kinase Plk1 regulates the function of mutant IDH1 and IDH2 in mitosis. Plk1 phosphorylates mutant IDH1 and IDH2, thereby controlling their enzyme activity and ubiquitination. These findings suggest that Plk1 could be a potential therapeutic target in mutant IDH-linked tumors.
CELLULAR SIGNALLING
(2022)
Article
Oncology
Tomohiko Ozaki, Manabu Kinoshita, Hideyuki Arita, Naoki Kagawa, Yasunori Fujimoto, Yonehiro Kanemura, Mio Sakai, Yoshiyuki Watanabe, Katsuyuki Nakanishi, Eku Shimosegawa, Jun Hatazawa, Haruhiko Kishima
Article
Oncology
Junya Fukai, Hideyuki Arita, Toru Umehara, Ema Yoshioka, Tomoko Shofuda, Daisuke Kanematsu, Yoshinori Kodama, Masayuki Mano, Manabu Kinoshita, Yoshiko Okita, Masahiro Nonaka, Takehiro Uda, Naohiro Tsuyuguchi, Daisuke Sakamoto, Yuji Uematsu, Naoyuki Nakao, Kanji Mori, Yonehiro Kanemura
BRAIN TUMOR PATHOLOGY
(2020)
Article
Neurosciences
Hideyuki Arita, Yuko Matsushita, Ryunosuke Machida, Kai Yamasaki, Nobuhiro Hata, Makoto Ohno, Shigeru Yamaguchi, Takashi Sasayama, Shota Tanaka, Fumi Higuchi, Toshihiko Iuchi, Kuniaki Saito, Masayuki Kanamori, Ken-ichiro Matsuda, Yohei Miyake, Kaoru Tamura, Sho Tamai, Taishi Nakamura, Takehiro Uda, Yoshiko Okita, Junya Fukai, Daisuke Sakamoto, Yasuhiko Hattori, Eriel Sandika Pareira, Ryusuke Hatae, Yukitomo Ishi, Yasuji Miyakita, Kazuhiro Tanaka, Shunsaku Takayanagi, Ryohei Otani, Tsukasa Sakaida, Keiichi Kobayashi, Ryuta Saito, Kazuhiko Kurozumi, Tomoko Shofuda, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Hikaru Sasaki, Masahiro Mizoguchi, Haruhiko Kishima, Mitsutoshi Nakada, Yukihiko Sonoda, Teiji Tominaga, Motoo Nagane, Ryo Nishikawa, Yonehiro Kanemura, Aya Kuchiba, Yoshitaka Narita, Koichi Ichimura
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2020)
Article
Oncology
Manabu Kinoshita, Hideyuki Arita, Masamichi Takahashi, Takehiro Uda, Junya Fukai, Kenichi Ishibashi, Noriyuki Kijima, Ryuichi Hirayama, Mio Sakai, Atsuko Arisawa, Hiroto Takahashi, Katsuyuki Nakanishi, Naoki Kagawa, Kouichi Ichimura, Yonehiro Kanemura, Yoshitaka Narita, Haruhiko Kishima
Summary: The study demonstrated that utilizing a TI shorter than 2,400 ms for FLAIR acquisition at 3T can enhance the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas.
FRONTIERS IN ONCOLOGY
(2021)
Article
Neuroimaging
Katsunori Asai, Hajime Nakamura, Yoshiyuki Watanabe, Takeo Nishida, Mio Sakai, Atsuko Arisawa, Masatoshi Takagaki, Hideyuki Arita, Tomohiko Ozaki, Naoki Kagawa, Yasunori Fujimoto, Katsuyuki Nakanishi, Manabu Kinoshita, Haruhiko Kishima
Summary: In preoperative embolization for intracranial meningioma, endovascular intratumoral embolization was found to be more effective in reducing tumor blood flow compared to proximal feeder occlusion, as assessed by DSC-PWI. The type of embolic material used did not significantly affect the reduction in tumor blood volume.
JOURNAL OF NEUROINTERVENTIONAL SURGERY
(2021)
Article
Oncology
Yusuke Funakoshi, Nobuhiro Hata, Kosuke Takigawa, Hideyuki Arita, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Yutaka Fujioka, Aki Sako, Toru Umehara, Tadamasa Yoshitake, Osamu Togao, Akio Hiwatashi, Koji Yoshimoto, Toru Iwaki, Masahiro Mizoguchi
Summary: The study revealed that CDKN2A homozygous deletion had no significant impact on OS for patients with methylated MGMT status, but significantly affected OS for patients with unmethylated MGMT status. The impact of CDKN2A homozygous deletion on OS was more pronounced in the pre-BEV era, but became nonsignificant in the post-BEV era due to OS improvement in patients with this genetic marker.
Article
Oncology
Satoshi Takahashi, Masamichi Takahashi, Manabu Kinoshita, Mototaka Miyake, Risa Kawaguchi, Naoki Shinojima, Akitake Mukasa, Kuniaki Saito, Motoo Nagane, Ryohei Otani, Fumi Higuchi, Shota Tanaka, Nobuhiro Hata, Kaoru Tamura, Kensuke Tateishi, Ryo Nishikawa, Hideyuki Arita, Masahiro Nonaka, Takehiro Uda, Junya Fukai, Yoshiko Okita, Naohiro Tsuyuguchi, Yonehiro Kanemura, Kazuma Kobayashi, Jun Sese, Koichi Ichimura, Yoshitaka Narita, Ryuji Hamamoto
Summary: The study proposed a method to address the issue of image differences among facilities causing performance degradation in automated magnetic resonance image segmentation for glioma detection. The results showed significant differences in the performance of the models developed using different datasets, with the fine-tuning model achieving the highest Dice coefficient score.
Article
Clinical Neurology
Kenji Fujimoto, Hideyuki Arita, Kaishi Satomi, Kai Yamasaki, Yuko Matsushita, Taishi Nakamura, Yasuji Miyakita, Toru Umehara, Keiichi Kobayashi, Kaoru Tamura, Shota Tanaka, Fumi Higuchi, Yoshiko Okita, Yonehiro Kanemura, Junya Fukai, Daisuke Sakamoto, Takehiro Uda, Ryunosuke Machida, Aya Kuchiba, Taketoshi Maehara, Motoo Nagane, Ryo Nishikawa, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Yoshitaka Narita, Koichi Ichimura
Summary: This study found that in IDH-wildtype lower grade gliomas, the pTERT mutation is a significant predictor of poor prognosis, while both EGFR amplification and PDGFRA gain also play important roles in prognosis.
ACTA NEUROPATHOLOGICA
(2021)
Review
Oncology
Hideyuki Arita, Koichi Ichimura
Summary: TERT promoter mutations in adult-type diffuse gliomas have significant diagnostic and prognostic value, particularly when combined with other molecular alterations to provide a more accurate prediction of patient outcomes.
BRAIN TUMOR PATHOLOGY
(2022)
Article
Oncology
Tomoyuki Nakano, Kenji Fujimoto, Arata Tomiyama, Masamichi Takahashi, Takamune Achiha, Hideyuki Arita, Daisuke Kawauchi, Mami Yasukawa, Kenkichi Masutomi, Akihide Kondo, Yoshitaka Narita, Taketoshi Maehara, Koichi Ichimura
Summary: Eribulin demonstrated strong inhibitory effects on cell proliferation, induced apoptosis, and suppressed cell migration in malignant meningioma cell lines, leading to significantly prolonged survival in orthotopic xenograft mouse models.
Article
Oncology
Toru Umehara, Hideyuki Arita, Fuyuki Miya, Takamune Achiha, Tomoko Shofuda, Ema Yoshioka, Daisuke Kanematsu, Tomoyoshi Nakagawa, Manabu Kinoshita, Naoki Kagawa, Yasunori Fujimoto, Naoya Hashimoto, Hiroki Kiyokawa, Eiichi Morii, Tatsuhiko Tsunoda, Yonehiro Kanemura, Haruhiko Kishima
Summary: This article describes a rare case in which a locally re-emerging glioma did not share genetic alterations with the primary tumor. Genetic sequencing revealed that mutations in the primary tumor disappeared in the re-emerging tumor, while new mutations were detected. This suggests that the initial and re-emerging tumors did not have a common origin.
BRAIN TUMOR PATHOLOGY
(2022)
Review
Surgery
Yukiko Seto, Nobuyoshi Kittaka, Azusa Taniguchi, Haruka Kanaoka, Satomi Nakajima, Yuri Oyama, Hiroki Kusama, Noriyuki Watanabe, Saki Matsui, Minako Nishio, Fumie Fujisawa, Koji Takano, Hideyuki Arita, Takahiro Nakayama
Summary: This article presents a case of PEG-induced vasculitis complicated by subarachnoid hemorrhage (SAH) in a breast cancer patient and reviews relevant literature. Although rare, vasculitis affecting vessels of various sizes may be caused by PEG.
SURGICAL CASE REPORTS
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Mio Sakai, Nobuo Kashiwagi, Katsuyuki Nakanishi, Noboru Maeda, Yasuhiro Nakaya, Junichiro Tanaka, Shinichiro Watanabe, Hidenari Hongyo, Yu Tanaka, Sawaka Yamada, Atsushi Kawata, Sou Toda, Koji Takano, Hideyuki Arita, Noriyuki Tomiyama
Summary: This review discusses the MRI findings of nonbrain metastases and emphasizes the importance of evaluating cranial and intracranial lesions, as well as considering direct geographical invasion, perineural spread, and double cancers.
JAPANESE JOURNAL OF RADIOLOGY
(2023)
Article
Clinical Neurology
Yu-ichiro Ohnishi, Nobuhiko Nakajima, Sho Fujiwara, Takashi Moriwaki, Hideyuki Arita, Haruhiko Kishima
Article
Clinical Neurology
Tomoyoshi Nakagawa, Hideyuki Arita, Noriyuki Kijima, Jiro Fujita, Yasuhiro Nagate, Ryuichi Hirayama, Manabu Kinoshita, Naoki Kagawa, Haruhiko Kishima
INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT
(2020)
