title: TERT promoter mutated WHO grades II and III gliomas are located preferentially in the frontal lobe and avoid the midline.
abstract: The promoter region of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase (IDH) have been regarded as biomarkers with distinct clinical and phenotypic features. Investigated the possible correlations between tumor location and genetic alterations would enhance our understanding of gliomagenesis and heterogeneity of glioma. We examined mutations of TERTp and IDH by direct sequencing and fluorescence in-situ hybridization in a cohort of 225 grades II and III diffuse gliomas. Correlation analysis between molecular markers and tumor locations was performed by Chi-square tests/Fisher's exact test and multivariate logistic regression analysis. We found gliomas in frontal lobe showed higher frequency of TERTp mutation (P=0.0337) and simultaneously mutations of IDH and TERTp (IDH (mut)-TERTp(mut)) (P=0.0281) than frequency of biomarkers mutation of tumors in no-Frontal lobes, while lower frequency of TERTp mutation (P<0.0001) and simultaneously wild type of IDH and TERTp (IDH (wt)-TERTp(wt)) (P<0.0001) in midline than no-midline lobes. Logistic regression analysis indicated that locations of tumors associated with TERTp mutation (OR=0.540, 95% CI 0.324-0.900, P=0.018) and status of combinations of IDH and TERTp (IDH (mut)-TERTp (mut) vs. IDH (wt)-TERTp (wt) OR=0.162, 95% CI 0.075-0.350, P<0.001). In conclusion, grades II and III gliomas harboring TERTp mutation were located preferentially in the frontal lobe and rarely in midline. Association of IDH-TERTp status and tumor location suggests their potential values in molecular classification of grades II and III gliomas.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China ; Department of Neurosurgery, North China University of Science and Technology Affiliated Hospital Tangshan 063000, Hebei Province, China ; Neurosurgical Immunology Laboratory of Huashan Hospital, Fudan University Shanghai, Chian.
authors.forename: Ze-Lin
authors.initials: ZL
authors.lastname: Sun
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong, China.
authors.forename: Aden Ka-Yin
authors.initials: AK
authors.lastname: Chan
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China ; Neurosurgical Immunology Laboratory of Huashan Hospital, Fudan University Shanghai, Chian.
authors.forename: Ling-Chao
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China ; Neurosurgical Immunology Laboratory of Huashan Hospital, Fudan University Shanghai, Chian.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000, China.
authors.forename: Chong-Ran
authors.initials: CR
authors.lastname: Sun
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China ; Neurosurgical Immunology Laboratory of Huashan Hospital, Fudan University Shanghai, Chian.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Liang-Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D014944:World Health Organization
chemical_list: D007521:Isocitrate Dehydrogenase; C509186:TERT protein, human; D019098:Telomerase
keywords: Gliomas; IDH mutation; TERT promoter mutation; heterogeneity; tumor location