Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system

Sayaka Yuzawa, Hiroshi Nishihara, Shigeru Yamaguchi, Hiromi Mohri, Lei Wang, Taichi Kimura, Masumi Tsuda, Mishie Tanino, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin, Norihiro Sato, Shinya Tanaka

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Recent genetic analyses using next-generation sequencers have revealed numerous genetic alterations in various tumors including meningioma, which is the most common primary brain tumor. However, their use as routine laboratory examinations in clinical applications for tumor genotyping is not cost effective. To establish a clinical sequencing system for meningioma and investigate the clinical significance of genotype, we retrospectively performed targeted amplicon sequencing on 103 meningiomas and evaluated the association with clinicopathological features. We designed amplicon-sequencing panels targeting eight genes including NF2 (neurofibromin 2), TRAF7, KLF4, AKT1, and SMO. Libraries prepared with genomic DNA extracted from PAXgene-fixed paraffin-embedded tissues of 103 meningioma specimens were sequenced using the Illumina MiSeq. NF2 loss in some cases was also confirmed by interphase-fluorescent in situ hybridization. We identified NF2 loss and/or at least one mutation in NF2, TRAF7, KLF4, AKT1, and SMO in 81 out of 103 cases (79%) by targeted amplicon sequencing. On the basis of genetic status, we categorized meningiomas into three genotype groups: NF2 type, TRAKLS type harboring mutation in TRAF7, AKT1, KLF4, and/or SMO, and 'not otherwise classified' type. Genotype significantly correlated with tumor volume, tumor location, and magnetic resonance imaging findings such as adjacent bone change and heterogeneous gadolinium enhancement, as well as histopathological subtypes. In addition, multivariate analysis revealed that genotype was independently associated with risk of recurrence. In conclusion, we established a rapid clinical sequencing system that enables final confirmation of meningioma genotype within 7 days turnaround time. Our method will bring multiple benefits to neuropathologists and neurosurgeons for accurate diagnosis and appropriate postoperative management.

Original languageEnglish
Pages (from-to)708-716
Number of pages9
JournalModern Pathology
Volume29
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1
Externally publishedYes

Fingerprint

Neurofibromin 2
Meningioma
Genotype
Neoplasms
Mutation
Gene Targeting
Interphase
Gadolinium
Tumor Burden
Fluorescence In Situ Hybridization
Brain Neoplasms
Paraffin
Libraries
Multivariate Analysis
Magnetic Resonance Imaging
Costs and Cost Analysis
Bone and Bones
Recurrence
DNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system. / Yuzawa, Sayaka; Nishihara, Hiroshi; Yamaguchi, Shigeru; Mohri, Hiromi; Wang, Lei; Kimura, Taichi; Tsuda, Masumi; Tanino, Mishie; Kobayashi, Hiroyuki; Terasaka, Shunsuke; Houkin, Kiyohiro; Sato, Norihiro; Tanaka, Shinya.

In: Modern Pathology, Vol. 29, No. 7, 01.07.2016, p. 708-716.

Research output: Contribution to journalArticle

Yuzawa, S, Nishihara, H, Yamaguchi, S, Mohri, H, Wang, L, Kimura, T, Tsuda, M, Tanino, M, Kobayashi, H, Terasaka, S, Houkin, K, Sato, N & Tanaka, S 2016, 'Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system', Modern Pathology, vol. 29, no. 7, pp. 708-716. https://doi.org/10.1038/modpathol.2016.81
Yuzawa, Sayaka ; Nishihara, Hiroshi ; Yamaguchi, Shigeru ; Mohri, Hiromi ; Wang, Lei ; Kimura, Taichi ; Tsuda, Masumi ; Tanino, Mishie ; Kobayashi, Hiroyuki ; Terasaka, Shunsuke ; Houkin, Kiyohiro ; Sato, Norihiro ; Tanaka, Shinya. / Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system. In: Modern Pathology. 2016 ; Vol. 29, No. 7. pp. 708-716.
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