Short postoperative survival for glioblastoma patients with a dysfunctional Rb1 pathway in combination with no wild-type PTEN.
OBJECTIVE
Glioblastoma (GB, WHO grade IV) is the most common primary brain tumor in adults. Survival is typically <1 year but varies between a few months and a couple of years. The aim of the study was to find novel genetic prognostic factors in a well-defined GB series.


METHODS
The survival data on 129 GBs were correlated with the results of a detailed analysis of 9 genes. These included 3 genes coding for proteins in the p53 pathway (i.e., TP53, p14(ARF), and MDM2), 4 in the Rb1 pathway (i.e., CDKN2A, CDKN2B, RB1, and CDK4), as well as PTEN and epidermal growth factor receptor.


RESULTS
We found that abnormalities in any of the four genes (CDKN2A, CDKN2B, RB1, and CDK4) coding for components of the Rb1 pathway were associated with shorter survival (P = 0.002). In combination with loss of wild-type PTEN, the association was even stronger (P < 0.001), the median survival being 166 days as compared with the group without these abnormalities where the median postoperative survival was 437 days. The survival difference remained statistically significant in Cox' regression analysis adjusting for age (P = 0.012).


CONCLUSIONS
The findings indicate that knowledge of the molecular genetic abnormalities in GBs provides important data in assessing individual patients. As additional advances in our understanding of the molecular genetics and cell biology of gliomas are made, in addition to providing prognostic information, such data may also provide targets for innovative therapy in the individual case.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D002648:Child; D005260:Female; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics*; D016019:Survival Analysis; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human