Kagoshima University · Graduate School of Medical and Dental Sciences

Research keywordscancer genomics・liquid cytology・KRAS variants・promoter methylation・molecular pathology・tumor sequencing

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• Okada T., Natsumeda M., Fujiwara H., Higa N., Akahane T., Watabe Y., Tomikawa K., Nishita K., Tsukamoto Y., Ohshima S., Horii A., Tanimoto A., Hanaya R., Shimizu H., Kakita A., Oishi M. . Case2025 · 記述言語： 日本語 出版者・発行元： Frontiers in Oncology Introduction: Brain stem gliomas harboring IDH mutations can be sensitive to temozolomide (TMZ) treatment, unlike their H3K27-altered counterparts, so distinguishing the two is essential. Case presentation: Here, we report an adult brainstem glioma patient whose hearing loss normalized after treatment. He presented with gradual left hearing loss from two years before, and magnetic resonance (MR) images showed a diffuse mass lesion involving the pons to left middle cerebral peduncle, including the vestibular and cochlear nuclei. On MR spectroscopy (MRS), 2-hydroxyglutarate (2HG) was elevated to 3.602 mM, suggesting an IDH-mutant glioma. Subsequently, an open biopsy was performed via the lateral suboccipital approach, and the pathological diagnosis was astrocytoma, IDH-mutant, CNS WHO grade 3. Molecular analysis revealed a non-canonical IDH2 R172S mutation. Left hearing improved from 87.5 dB to 8.3dB by 6-frequency pure tone audiogram (PTA) and 90% speech discrimination at 35 dB after concomitant TMZ and radiation treatment, followed by 12 cycles of adjuvant TMZ treatment. 2HG also decreased to 0.186 mM on MRS after treatment determining treatment strategy. Discussion: Studies have shown that as high as 31% of adult brainstem gliomas are IDH mutant, with most of these mutations being non-canonical IDH1/2 mutations. Approximately 70% of IDH-mutant astrocytomas are known to harbor a methylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter and respond to TMZ treatment, whereas almost all H3K27M-mutant diffuse midline gliomas have unmethylated MGMT promoters and generally are not sensitive to TMZ treatment. Detection of 2HG by MRS and molecular analysis, including non-canonical IDH1/2 mutations, were helpful in determining treatment response in this adult brainstem glioma case. Notably, hearing loss normalized after TMZ treatment. Conclusion: The diagnosis of IDH-mutant brainstem gliomas by MRS and integrated analysis of surgically obtained specimens is essential to determine the proper treatment of these rare cases. DOI： 10.3389/fonc.2025.1555986 Scopus PubMed
• Makino Ryutaro, Bajagain Madan, Higa Nayuta, Akahane Toshiaki, Yonezawa Hajime, Uchida Hiroyuki, Takajo Tomoko, Kirishima Mari, Yokoyama Seiya, Otsuji Ryosuke, Fujioka Yutaka, Kuga Daisuke, Yamahata Hitoshi, Kurosaki Masamichi, Yamamoto Junkoh, Yoshimoto Koji, Tanimoto Akihide, Hanaya Ryosuke2025 · 記述言語： 英語 出版者・発行元： 日本脳腫瘍病理学会
• Fukuda K., Hozaka Y., Oi H., Tomita M., Idichi T., Yamasaki Y., Kawasaki Y., Hayashi Y., Goto Y., Sugiura T., Akahane T., Higashi M., Tanimoto A., Ohtsuka T. . Association between intra-tumora2025 · 記述言語： 日本語 出版者・発行元： Pancreatology Background/objectives: We previously demonstrated that intra-tumoral microbiome infection may affects the clinicopathological characteristics of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and showed that these characteristics are also influenced by gene mutations. The aim of this study was to investigate whether specific microbiome infections lead to alterations in the expression of specific genes in IPMNs. Methods: DNA was extracted from 26 resected IPMN samples and subjected to genetic mutation assessment and microbiome analysis. The relationship between intra-tumoral microbiome and genetic alterations was investigated. Results: There was an increasing trend in the percentage of Firmicutes in KRAS- and GNAS-mutated IPMNs, whereas Proteobacteria tended to decrease in KRAS-mutated IPMNs. KLF4-mutated IPMNs, particularly within the KRAS-mutated group, had significantly low α-diversity (p < 0.05). The relative abundance of Firmicutes and Proteobacteria was significantly higher in KLF4-mutated IPMNs, especially in KLF4-mutated IPMNs among the KRAS-mutated groups. An increased relative abundance of Firmicutes and Proteobacteria, along with the associated reduction in microbial diversity, was associated with a higher frequency of gene mutations, including KLF4. Conclusions: This study suggest that the intratumoral microbiome may be linked to the genetic characteristics of IPMNs and potentially contribute to their malignant progression. DOI： 10.1016/j.pan.2025.08.001 Scopus PubMed
• Nagamine Y., Tomita M., Yamakuchi M., Hozaka Y., Okumura T., Oi H., Fukuda K., Idichi T., Yamasaki Y., Mataki Y., Kawasaki Y., Akahane T., Higashi M., Hashiguchi T., Tanimoto A., Ohtsuka T. .2025 · 記述言語： 日本語 出版者・発行元： Pancreatology Background/Objectives Krüppel-like factor 4 (KLF4) hotspot mutations are linked to non-invasive intraductal papillary mucinous neoplasms (IPMNs); however, the molecular mechanisms driving their progression remain unclear. Therefore, in this study, we aimed to identify the signaling pathways associated with KLF4 mutations and their roles in IPMNs. Methods Thirty-three resected specimens of IPMNs were collected. Associations between genetic alterations in KLF4 and the expression levels of KLF4 protein as well as its related signaling proteins, including p21, p27, and cyclin D, were assessed. Results KLF4 mutations were found in eight specimens of IPMNs (24 %), all of which were non-invasive lesions and non-intestinal type; of them, seven (87.5 %) showed GNAS mutations. p21 expression was significantly elevated in KLF4 -mutated IPMNs (p < 0.01), whereas p27 and cyclin D1 levels were not significantly altered compared with KLF4 wild-type IPMNs. KLF4 and p21 expression levels were significantly elevated in non-invasive lesions compared with invasive lesions (p < 0.05). Higher KLF4 expression was observed in GNAS- mutated IPMNs than in GNAS wild-type IPMNs (p < 0.05). Conclusions KLF4 mutations might enhance p21 expression, possibly influencing the indolent characteristics of non-invasive IPMNs and providing a new biomarker strategy for risk stratification in patients with IPMNs. DOI： 10.1016/j.pan.2025.09.028 Scopus PubMed

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