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IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas
Ist Teil von
International journal of clinical oncology, 2012-12, Vol.17 (6), p.551-561
Ort / Verlag
Japan: Springer Japan
Erscheinungsjahr
2012
Quelle
MEDLINE
Beschreibungen/Notizen
Background
The discovery of isocitrate dehydrogenase 1 and 2 gene (
IDH1/2
) mutations has enabled grade III glioma to be divided into mutated and wild-type
IDH1/2
groups, which are known to carry different prognosis and molecular features. However, detailed subgroup analysis of grade III glioma is limited. To address this, we investigated molecular and prognostic features of grade III glioma with and without
IDH1/2
mutation.
Methods
We retrospectively analyzed 115 grade III glioma patients. Clinical parameters were obtained from medical records. The mutation of
IDH1/2
and
TP53
was analyzed by direct sequencing. O
6
-methylguanine methyltransferase gene (
MGMT
) gene promoter methylation status was determined by methylation-specific polymerase chain reaction. Detection of chromosome copy number changes of 1p, 7p (
EGFR
), 9p (
CDKN2A
), 10q (
PTEN)
, and 19q was carried out by multiple ligation-dependent probe amplification. Patients were divided into two groups, mutated
IDH1/2
and wild-type
IDH1/2
, for correlation with the factors analyzed.
Results
In our series, as previously reported,
IDH1/2
mutation was an independent prognostic marker for improved progression-free and overall survival (OS) (
P
< 0.0001 and
P
< 0.0001, respectively) in patients with grade III gliomas. Subgroup analysis found that incomplete resection, 7p gain, and
TP53
mutation were independent prognostic factors of poor outcome in grade III glioma patients with mutated
IDH1/2
(
P
= 0.0092,
P
= 0.015 and
P
= 0.026, respectively), while there were none in patients with wild-type
IDH1/2
.
Conclusions
IDH1/2
gene status was significantly associated with prognosis in grade III gliomas. Subgroup analysis found that poor prognostic factors existed even in patients with
IDH1/2
mutation.