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学科主题基础医学
ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients
Shao, Li-Wei1; Pan, Yi1; Qi, Xue-Ling2; Li, Yong-Xiao1; Ma, Xiao-Long1; Yi, Wei-Ning3; Zhang, Jing1,4; Zhong, Yan-Feng1; Chang, Qing1
关键词Atrx P53 Idh1 Mgmt Immunohistochemistry Fluorescence In Situ Hybridization
刊名HISTOLOGY AND HISTOPATHOLOGY
2016
31期:1页:103-114
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Pathology
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Cell Biology ; Pathology
关键词[WOS]GENE O-6-METHYLGUANINE-DNA METHYLTRANSFERASE ; CENTRAL-NERVOUS-SYSTEM ; PROMOTER HYPERMETHYLATION ; ANAPLASTIC GLIOMAS ; GRADE-II ; CLASSIFICATION ; TUMORS ; SURVIVAL ; ANTIBODY ; BRAIN
英文摘要

Background: IDH1/2 mutation, 1p/19q-codeletion and MGMT hypermethylation are well known molecular markers for gliomas. ATRX and p53 alterations are two lineage-specific genetic aberrations in diffuse astrocytic tumors. The aim of the present study is to clarify the significance of ATRX loss and its correlation with p53 overexpression, IDH1/2 mutations, 1p/19q-codeletion and MGMT hypermethylation in supertentorial astrocytoma, and to determine the prognostic value of these factors in Chinese patients. Methods and Results: A total of 135 adult supertentorial astrocytomas were evaluated. ATRX loss was detected by immunohistochemistry (IHC) and was shown to be much less frequent in pGBs (3.5%) than in grade II, III astrocytomas and IV sGBs (31%). Direct sequencing and/or IHC analysis of the IDH1R132H gene mutation and p53 accumulation demonstrated correlation with age. Strong correlations were found between ATRX loss and IDH1R132H mutation, p53 overexpression as well as MGMT hypermethylation. 1p/19q-codeletion detected by fluorescence in situ hybridization (FISH) showed mutually exclusive with ATRX loss and p53 accumulation. In addition, patients with p53 overexpression combined with ATRX alterations demonstrated substantially longer survival than patients with wild-type ATRX. Conclusions: There may be interactions among these distinct molecules in astrocytoma development. ATRX loss may predict better clinical outcome in astrocytoma patients with p53 overexpression as compared to patients with wild-type ATRX. Tumors with astrocytoma phenotype accompanied by 1p/19q-codeletion and IDH1R132H mutation are mutually exclusive with ATRX and p53 alterations. Routine IHC can be used for evaluation of ATRX loss, p53 protein accumulation and IDH1R132H mutation, which may allow a means of classification of astrocytoma outcome.

语种英语
所属项目编号81101900
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000366337900010
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54405
专题基础医学院_病理学系
作者单位1.Peking Univ, Sch Basic Med Sci, Dept Pathol, Hosp 3, Beijing 100191, Peoples R China
2.Beijing Sanbo Brain Hosp, Dept Pathol, Beijing, Peoples R China
3.Peking Univ, Dept Epidemiol & Hlth Stat, Beijing 100191, Peoples R China
4.Univ Washington, Sch Med, Dept Neuropathol, Harborview Med Ctr, Seattle, WA 98104 USA
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Shao, Li-Wei,Pan, Yi,Qi, Xue-Ling,et al. ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients[J]. HISTOLOGY AND HISTOPATHOLOGY,2016,31(1):103-114.
APA Shao, Li-Wei.,Pan, Yi.,Qi, Xue-Ling.,Li, Yong-Xiao.,Ma, Xiao-Long.,...&Chang, Qing.(2016).ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients.HISTOLOGY AND HISTOPATHOLOGY,31(1),103-114.
MLA Shao, Li-Wei,et al."ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients".HISTOLOGY AND HISTOPATHOLOGY 31.1(2016):103-114.
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