Genomic Alteration Patterns Across Histological Grades in <i>BRAF</i> p.V600E‐Mutant Gliomas and Glioneuronal Tumors: An Analysis of 15 Cases

BRAF p.V600E-mutant gliomas and glioneuronal tumors comprise a wide clinicopathological spectrum, yet the relationship between genomic alteration burden and histological grade remains incompletely defined. We analyzed 15 BRAF p.V600E-mutant gliomas and glioneuronal tumors across histological grades using the PleSSision Rapid sequencing platform. Single-nucleotide variants (SNVs) and copy-number alterations were assessed in parallel to characterize genomic alteration profiles. Low-grade tumors generally exhibited limited genomic alterations; however, a subset of low-grade tumors showed increased numbers of SNVs. High-grade tumors demonstrated more extensive genomic alterations, characterized predominantly by copy-number gains. A trend toward increased copy-number gains with higher WHO grade was observed. Homozygous deletion of CDKN2A was observed in pleomorphic xanthoastrocytoma, including both CNS WHO grade 2 and grade 3 tumors, and epithelioid glioblastoma. These findings indicate substantial genomic heterogeneity among BRAF p.V600E-mutant gliomas and glioneuronal tumors. While low-grade tumors are generally genomically quiet, a subset shows increased alterations, and high-grade tumors tend to acquire copy-number changes, highlighting the limitations of genomic event counts alone as a surrogate for malignant potential.

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Journal
Pathology International
Published
2026-04-01
DOI
https://doi.org/10.1111/pin.70113
Primary Topic
Glioma Diagnosis and Treatment
Type
article
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article

Genomic Alteration Patterns Across Histological Grades in BRAF p.V600E‐Mutant Gliomas and Glioneuronal Tumors: An Analysis of 15 Cases

Mina Ikeda, Ryuta Saito, Kosuke Aoki, Junya Yamaguchi et al.
Pathology International
Glioma Diagnosis and Treatment
article

Genomic Alteration Patterns Across Histological Grades in BRAF p.V600E‐Mutant Gliomas and Glioneuronal Tumors: An Analysis of 15 Cases

Mina Ikeda, Ryuta Saito, Kosuke Aoki, Junya Yamaguchi, Kazuya Motomura, Shoichi Deguchi, Sachiko Minamiguchi, Seiji Yamada, Tetsuya Takimoto, Kennosuke Karube, Mayu Takeda, Eiji Sugihara, Shigeo Ohba, Fumiharu Ohka, Hideyuki Saya, Yuichi Hirose
article en

Abstract

BRAF p.V600E-mutant gliomas and glioneuronal tumors comprise a wide clinicopathological spectrum, yet the relationship between genomic alteration burden and histological grade remains incompletely defined. We analyzed 15 BRAF p.V600E-mutant gliomas and glioneuronal tumors across histological grades using the PleSSision Rapid sequencing platform. Single-nucleotide variants (SNVs) and copy-number alterations were assessed in parallel to characterize genomic alteration profiles. Low-grade tumors generally exhibited limited genomic alterations; however, a subset of low-grade tumors showed increased numbers of SNVs. High-grade tumors demonstrated more extensive genomic alterations, characterized predominantly by copy-number gains. A trend toward increased copy-number gains with higher WHO grade was observed. Homozygous deletion of CDKN2A was observed in pleomorphic xanthoastrocytoma, including both CNS WHO grade 2 and grade 3 tumors, and epithelioid glioblastoma. These findings indicate substantial genomic heterogeneity among BRAF p.V600E-mutant gliomas and glioneuronal tumors. While low-grade tumors are generally genomically quiet, a subset shows increased alterations, and high-grade tumors tend to acquire copy-number changes, highlighting the limitations of genomic event counts alone as a surrogate for malignant potential.

Pathology InternationalVol. 76(4)
Fujita Health University (JP), Shizuoka Cancer Center (JP), Nagoya University Hospital (JP), Nagoya University (JP), Aichi Shukutoku University (JP)
Good health and well-being
Openalex Percentile: Top 19%
Glioma Diagnosis and Treatment
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