Mutations of PTEN gene in gliomas correlate to tumor differentiation and short-term survival rate.
The present study determined mutations of phosphatase and tensin homolog (PTEN) gene in patients suffering from high-grade gliomas (WHO grades III and IV) and further investigated the mutations in correlation to patients' histopathological classification and short-term survival. Total RNA and genomic DNA were extracted from tumor tissues. Full-length PTEN cDNA sequences were amplified by polymerase chain reaction (PCR). The PCR products were directly sequenced, and the PTEN mutations were analyzed. It demonstrated that the incidence of PTEN mutations was 8/22 in these patients: one patient with WHO grade III glioma (1/11) and 7 patients with WHO grade IV glioma (7/11). Most patients had three or more mutations in the PTEN gene, with exons 2, 3, 4, 5, 6 and 7 as hot mutation regions, with mutation incidence from 62.5% to 75%. About 68.4% of mutations were missense, 26.3% same-sense and 5.3% nonsense mutations. The median survival times of the WHO grade III and IV groups were 250 and 53 weeks after surgery, respectively (p=0.016). The 36-week survival rate of patients with and without PTEN mutations was 62.5% and 92.9% (p=0.038, odds ratio=7.80), respectively. The present study suggests that PTEN mutations are late events in the malignant progression of glioma and the occurrence of PTEN mutations are significantly correlated to patients' short-term survival.
Yang
Yiling
Y
Section of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lunds University, S-221 85 Lund, Sweden.
Shao
Naiyuan
N
Luo
Guanghua
G
Li
Lu
L
Zheng
Lu
L
Nilsson-Ehle
Peter
P
Xu
Ning
N
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D005838:Genotype; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D015996:Survival Rate
D018389:Codon, Nonsense; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human