PMID- 19755387
OWN - NLM
STAT- MEDLINE
DCOM- 20091222
LR  - 20220410
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 19
DP  - 2009 Oct 1
TI  - IDH1 mutations as molecular signature and predictive factor of secondary 
      glioblastomas.
PG  - 6002-7
LID - 10.1158/1078-0432.CCR-09-0715 [doi]
AB  - PURPOSE: To establish the frequency of IDH1 mutations in glioblastomas at a 
      population level, and to assess whether they allow reliable discrimination 
      between primary (de novo) glioblastomas and secondary glioblastomas that 
      progressed from low-grade or anaplastic astrocytoma. EXPERIMENTAL DESIGN: We 
      screened glioblastomas from a population-based study for IDH1 mutations and 
      correlated them with clinical data and other genetic alterations. RESULTS: IDH1 
      mutations were detected in 36 of 407 glioblastomas (8.8%). Glioblastoma patients 
      with IDH1 mutations were younger (mean, 47.9 years) than those with EGFR 
      amplification (60.9 years) and were associated with significantly longer survival 
      (mean, 27.1 versus 11.3 months; P < 0.0001). IDH1 mutations were frequent in 
      glioblastomas diagnosed as secondary (22 of 30; 73%), but rare in primary 
      glioblastomas (14 of 377; 3.7%: P < 0.0001). IDH1 mutations as genetic marker of 
      secondary glioblastoma corresponded to the respective clinical diagnosis in 95% 
      of cases. Glioblastomas with IDH1 mutation diagnosed as primary had clinical and 
      genetic profiles similar to those of secondary glioblastomas, suggesting that 
      they may have rapidly progressed from a less malignant precursor lesion that 
      escaped clinical diagnosis and were thus misclassified as primary. Conversely, 
      glioblastomas without IDH1 mutations clinically diagnosed as secondary typically 
      developed from anaplastic rather than low-grade gliomas, suggesting that at least 
      some were actually primary glioblastomas, that may have been misclassified, 
      possibly due to histologic sampling error. CONCLUSION: IDH1 mutations are a 
      strong predictor of a more favorable prognosis and a highly selective molecular 
      marker of secondary glioblastomas that complements clinical criteria for 
      distinguishing them from primary glioblastomas.
FAU - Nobusawa, Sumihito
AU  - Nobusawa S
AD  - International Agency for Research on Cancer, Lyon, France.
FAU - Watanabe, Takuya
AU  - Watanabe T
FAU - Kleihues, Paul
AU  - Kleihues P
FAU - Ohgaki, Hiroko
AU  - Ohgaki H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090915
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Biomarkers, Tumor)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Astrocytoma/diagnosis/genetics/mortality/*pathology
MH  - Base Sequence
MH  - Biomarkers, Tumor/genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Expression Profiling
MH  - Glioblastoma/*diagnosis/genetics/*secondary
MH  - Humans
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/physiology
MH  - Nervous System Neoplasms/diagnosis/genetics/mortality/*pathology
MH  - Prognosis
MH  - Survival Analysis
EDAT- 2009/09/17 06:00
MHDA- 2009/12/23 06:00
CRDT- 2009/09/17 06:00
PHST- 2009/09/17 06:00 [entrez]
PHST- 2009/09/17 06:00 [pubmed]
PHST- 2009/12/23 06:00 [medline]
AID - 1078-0432.CCR-09-0715 [pii]
AID - 10.1158/1078-0432.CCR-09-0715 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Oct 1;15(19):6002-7. doi: 10.1158/1078-0432.CCR-09-0715. 
      Epub 2009 Sep 15.