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Open Access 01-12-2021 | Glioblastoma | Research

Infrequent RAS mutation is not associated with specific histological phenotype in gliomas

Authors: Yasuhide Makino, Yoshiki Arakawa, Ema Yoshioka, Tomoko Shofuda, Sachiko Minamiguchi, Takeshi Kawauchi, Masahiro Tanji, Daisuke Kanematsu, Masahiro Nonaka, Yoshiko Okita, Yoshinori Kodama, Masayuki Mano, Takanori Hirose, Yohei Mineharu, Susumu Miyamoto, Yonehiro Kanemura

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas.

Methods

This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis.

Results

RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology.

Conclusion

RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.

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Title: Infrequent RAS mutation is not associated with specific histological phenotype in gliomas
Authors: Yasuhide Makino
Yoshiki Arakawa
Ema Yoshioka
Tomoko Shofuda
Sachiko Minamiguchi
Takeshi Kawauchi
Masahiro Tanji
Daisuke Kanematsu
Masahiro Nonaka
Yoshiko Okita
Yoshinori Kodama
Masayuki Mano
Takanori Hirose
Yohei Mineharu
Susumu Miyamoto
Yonehiro Kanemura
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Glioblastoma
Astrocytoma
Glioma
Glioma
Astrocytoma
Glioblastoma
Astrocytoma
Glioblastoma
Oligodendroglioma
Glioma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08733-4

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