Variant of the CHEK2 gene as a prognostic marker in glioblastoma multiforme.
OBJECTIVE
Germline mutations of the CHEK2 tumor suppressor gene have been found in families with the Li-Fraumeni syndrome (LFS). Patients with LFS experience a variety of cancers, including malignant astrocytomas. We investigated a potential role for a CHEK2 gene polymorphism in glioblastomas.


METHODS
A genetic polymorphism of the CHEK2 gene (CHEK2 SNP rs2017309 A/T) was genotyped in a series of glioblastoma patients (n = 213) and population controls (n = 192). Subsets of tumors were analyzed for loss of heterozygosity 22q(n = 66), loss of heterozygosity CHEK2 (n = 53), CHEK2 expression (n = 21), and CHEK2 coding sequence alterations (n = 18). CHEK2 SNP rs2017309 genotyping findings and traditional clinicopathological parameters were correlated with the patients' prognoses.


RESULTS
No association between the CHEK2 SNP and glioblastoma formation was observed. No CHEK2 coding sequence aberrations or tumors completely lacking CHEK2 protein were identified. However, the presence of the CHEK2 rs2017309 A allele was significantly associated with an adverse prognosis (P = 0.034), particularly among patients undergoing postoperative chemotherapy and radiotherapy (n = 28, median survival 10.5 versus 15.5 mo, P = 0.008). We could confirm the patients' age, Karnofsky Performance Scale score, and postoperative radiotherapy and chemotherapy (all P < 0.0001, log-rank test) as decisive prognostic factors.


CONCLUSIONS
Our data suggest that a CHEK2 gene polymorphism might correlate with the prognosis of glioblastoma patients. These findings may point to an as yet unrecognized role for the CHEK2 gene in glioblastomas.
Simon
Matthias
M
Department of Neurosurgery, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. Matthias.Simon@ukb.uni-bonn.de
Ludwig
Michael
M
Fimmers
Rolf
R
Mahlberg
Ralph
R
Müller-Erkwoh
Angelika
A
Köster
Gertraud
G
Schramm
Johannes
J
D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D064447:Checkpoint Kinase 2; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D005909:Glioblastoma / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000097:blood* / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013223:Statistics as Topic; D016019:Survival Analysis; D015996:Survival Rate
D015415:Biomarkers; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases