title: Gene mutation profiling of primary glioblastoma through multiple tumor biopsy guided by 1H-magnetic resonance spectroscopy.
abstract: Genetic mutation has served as the biomarkers for the diagnosis and treatment of glioblastoma multiforme (GBM). However, intra-tumor heterogeneity may interfere with personalized treatment strategies based on mutation analysis. This study aimed to characterize somatic mutation profiling of GBM. We collected 33 samples from 7 patients with the primary GBM associated with different Choline (Cho) to N-acetylaspartate (NAA) index (CNI) through the frameless proton magnetic resonance spectroscopy (1H-MRS) guided biopsies and investigated multiple somatic mutations profiling using the AmpliSeq cancer hotspot panel V2. We identified 53 missense or nonsense mutations in 27 genes including some novel mutations such as APC and IDH2. The mutations in EGFR, TP53, PTEN, PIK3CA genes were presented with different frequency and the majority of the mutated gene was only shared by 1-2 samples from one patient. Moreover, we found the association of CNI with histological grade, but there was no significant change of CNI in the presence of TP53, EGFR and PTEN mutations. These data suggest that gene mutations constitute a heterogeneous marker for primary GBM which may be independent of intra-tumor morphological phenotypes of GBM; therefore, gene mutation markers could not be determined from a small number of needle biopsies or only confined to the high-grade region.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Dong-Xiao
authors.initials: DX
authors.lastname: Zhuang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, Huashan Hospital,Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Tang
authors.affiliation: Department of Radiology, Huashan Hospital,Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University Shanghai 200040, China.
authors.forename: Liang-Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002794:Choline / Q000032:analysis; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D060787:Neoplasm Grading; D010641:Phenotype; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018389:Codon, Nonsense; D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline
keywords: Mutation profi ling; biopsy; glioblastoma multiforme; heterogeneity; proton magnetic resonance spectroscopy