Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression.
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.


CONCLUSIONS
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.
Hoang-Xuan
K
K
Biologie des interactions neurone-glie, INSERM U495 et Université P. et M. Curie, Federation Neurologique Mazarin, Groupe hospitalier Pitié-Salpêtrière, Paris. khe.hoang-xuan@psl.ap-hop-paris.fr
He
J
J
Huguet
S
S
Mokhtari
K
K
Marie
Y
Y
Kujas
M
M
Leuraud
P
P
Capelle
L
L
Delattre
J Y
JY
Poirier
J
J
Broët
P
P
Sanson
M
M
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002888:Chromosomes, Human, Pair 19; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D019942:Genes, p16 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D018740:Genetic Heterogeneity; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D015999:Multivariate Analysis; D009837:Oligodendroglioma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human