PMID- 26395639
OWN - NLM
STAT- MEDLINE
DCOM- 20160920
LR  - 20221207
IS  - 1699-5848 (Electronic)
IS  - 0213-3911 (Linking)
VI  - 31
IP  - 1
DP  - 2016 Jan
TI  - ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over 
      expression and IDH1 mutation and predicts better outcome in p53 accumulated 
      patients.
PG  - 103-14
LID - 10.14670/HH-11-664 [doi]
AB  - 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.
FAU - Shao, Li-Wei
AU  - Shao LW
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing, China.
FAU - Pan, Yi
AU  - Pan Y
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing, China.
FAU - Qi, Xue-Ling
AU  - Qi XL
AD  - Department of Pathology, Beijing Sanbo Brain Hospital, Beijing, China.
FAU - Li, Yong-Xiao
AU  - Li YX
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing, China.
FAU - Ma, Xiao-Long
AU  - Ma XL
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing, China.
FAU - Yi, Wei-Ning
AU  - Yi WN
AD  - Department of Epidemiology and Health Statistics, Peking University, Beijing, 
      China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing, China and Department of Neuropathology, 
      Harborview Medical Center, University of Washington School of Medicine, Seattle, 
      WA, USA.
FAU - Zhong, Yan-Feng
AU  - Zhong YF
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing, China.
FAU - Chang, Qing
AU  - Chang Q
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University, Beijing. China qingchang@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150923
PL  - Spain
TA  - Histol Histopathol
JT  - Histology and histopathology
JID - 8609357
RN  - 0 (Nuclear Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - EC 2.1.1.63 (MGMT protein, human)
RN  - EC 3.6.4.- (DNA Helicases)
RN  - EC 3.6.4.12 (ATRX protein, human)
RN  - EC 3.6.4.12 (X-linked Nuclear Protein)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Asian People
MH  - Astrocytoma/*genetics
MH  - DNA Helicases/*genetics
MH  - DNA Modification Methylases/genetics
MH  - DNA Repair Enzymes/genetics
MH  - Female
MH  - Gene Deletion
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Neoplasm Grading
MH  - Nuclear Proteins/*genetics
MH  - Supratentorial Neoplasms/*genetics
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Tumor Suppressor Protein p53/*genetics
MH  - Tumor Suppressor Proteins/genetics
MH  - X-linked Nuclear Protein
MH  - Young Adult
EDAT- 2015/09/24 06:00
MHDA- 2016/09/22 06:00
CRDT- 2015/09/24 06:00
PHST- 2015/09/24 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/09/22 06:00 [medline]
AID - HH-11-664 [pii]
AID - 10.14670/HH-11-664 [doi]
PST - ppublish
SO  - Histol Histopathol. 2016 Jan;31(1):103-14. doi: 10.14670/HH-11-664. Epub 2015 Sep 
      23.