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Molecular
heterogeneity of oligodendrogliomas suggests alternative pathways in
tumor progression
Hoang-Xuan
K, He J, Huguet S, Mokhtari K, Marie Y, Kujas M, Leuraud P, Capelle L,
Delattre JY, Poirier J, Broet P, Sanson M
Biologie des interactions neurone-glie, INSERM U495 et Universite
P. et M. Curie, Federation Neurologique Mazarin, Groupe hospitalier
Pitie-Salpetriere, Paris. khe.hoang-xuan@psl.ap-hop-paris.fr
Objective. To identify different genetic molecular
profiles in oligodendrogliomas and to evaluate their prognostic
significance.
Methods.
The main genetic alterations reported in glial tumors were
investigated in 26 oligodendrogliomas (10 World Health Organization
grade II and 16 World Health Organization grade III).
Correlation
between identified molecular changes and pathologic grade or clinical
course was subsequently analyzed using univariate and multivariate
statistical analyses.
Results.
Loss of heterozygosity (LOH) on chromosome 1p, 19q, and 10; P16/CDKN2A
homozygous deletion; EGFR (epidermal growth factor receptor)
amplification; and TP53 and PTEN mutations were observed in 14 (54%),
15 (58%), 9 (35%), 7 (27%), 5 (19%), 1 (4%), and 0 cases.
LOH
1p and 19q were tightly associated (p < 0.0001).
A
mutual exclusion was found between LOH 1p/19q and EGFR amplification
(p = 0.01), P16/CDKN2A deletions (p = 0.001), or LOH on 10q (p =
0.03), suggesting the existence of distinct genetic subsets in
oligodendrogliomas.
On
univariate analysis, age <50 years (p = 0.002) and LOH 1p (p =
0.01) were associated with a longer progression-free survival (PFS)
whereas LOH 10q (p = 0.03) and EGFR amplification (p = 0.007) were
associated with a worse PFS.
In
multivariate analyses, age <50 years (p = 0.001) and LOH 1p (p =
0.006) remained independent predictive factors for PFS.
Conclusion.
These results provide evidence for two alternative molecular pathways
of progression in oligodendrogliomas.
The
first one is associated with loss of 1p and 19q and the second one
with P16/CDKN2A deletion, 10q loss, and EGFR amplification.
The
findings confirm the value of loss of 1p as predictor of longer
progression-free survival; in addition, the study demonstrates the
unfavorable impact of 10q loss and EGFR amplification on the
prognosis.
PMID: 11591848 [PubMed - indexed for MEDLINE]
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