PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis.
Allelic loss of 10q is a common genetic event in malignant gliomas, with three 10q tumor suppressor genes, ERCC6, PTEN, and DMBT1, putatively implicated in the most common type of malignant glioma, glioblastoma. Anaplastic oligodendroglioma, another type of malignant glioma, provides a unique opportunity to study the relevance of particular genetic alterations to chemosensitivity and survival. We therefore analyzed these three genes in 72 anaplastic oligodendrogliomas. Deletion mapping demonstrated 10q loss in 14 of 67 informative cases, with the PTEN and DMBT1 regions involved in all deletions but with the ERCC6 locus spared in two cases. Seven tumors had PTEN gene alterations; two had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. No mutations were found in ERCC6 exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTEN alterations, but with unexpected short survival times. PTEN gene alterations were not associated with poor therapeutic response in multivariate analysis, but were independently predictive of poor prognosis even after multivariate adjustment for both 10q and 1p loss. In anaplastic oligodendroglioma, therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with poor prognosis, even in chemosensitive cases.
Sasaki
H
H
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.
Zlatescu
M C
MC
Betensky
R A
RA
Ino
Y
Y
Cairncross
J G
JG
Louis
D N
DN
D000373:Agglutinins; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000502:physiology*; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes