Infrequent RAS mutation is not associated with specific histological phenotype in gliomas.
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.
['Makino|Yasuhide|Y|', 'Arakawa|Yoshiki|Y|', 'Yoshioka|Ema|E|', 'Shofuda|Tomoko|T|', 'Minamiguchi|Sachiko|S|', 'Kawauchi|Takeshi|T|', 'Tanji|Masahiro|M|', 'Kanematsu|Daisuke|D|', 'Nonaka|Masahiro|M|', 'Okita|Yoshiko|Y|', 'Kodama|Yoshinori|Y|', 'Mano|Masayuki|M|', 'Hirose|Takanori|T|', 'Mineharu|Yohei|Y|', 'Miyamoto|Susumu|S|', 'Kanemura|Yonehiro|Y|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D001254:Astrocytoma D001932:Brain Neoplasms D002648:Child D002675:Child, Preschool D019175:DNA Methylation D015254:DNA Modification Methylases D004252:DNA Mutational Analysis D045643:DNA Repair Enzymes D005091:Exons D005260:Female D011905:Genes, ras D005909:Glioblastoma D005910:Glioma D006657:Histones D006801:Humans D007521:Isocitrate Dehydrogenase D008297:Male D008875:Middle Aged D009154:Mutation D009837:Oligodendroglioma D010641:Phenotype D011401:Promoter Regions, Genetic D019098:Telomerase D025521:Tumor Suppressor Proteins D055815:Young Adult
RAS mutation Histological phenotype Glioma Oligodendroglioma Astrocytoma Ganglioglioma