MET gain in diffuse astrocytomas is associated with poorer outcome

Abstract

Glioblastoma may develop rapidly without evidence for precursor lesions (primary glioblastomas), or progress from diffuse or anaplastic astrocytomas (secondary glioblastomas). Despite having distinct genetic profiles, these glioblastoma subtypes have similar histological features. We hypothesized that the highly malignant phenotype of glioblastoma may be attributable to genetic alterations that are common to both glioblastoma subtypes. In the present study, we first searched for commonly (>35%) amplified genes in glioblastomas with IDH1 mutation (a hallmark of secondary glioblastoma) and those without IDH1 mutation (typical for primary glioblastoma) in data from The Cancer Genome Atlas (TCGA). A total of 25 genes were identified, of which 21 were located at 7q31-34. We then screened 264 gliomas (70 glioblastomas, 112 diffuse astrocytomas, 82 oligodendrogliomas) for gain of the MET at 7q31.2 with quantitative polymerase chain reaction (PCR). MET gain was detected in primary glioblastomas (47%) and secondary glioblastomas (44%), suggesting that this genetic alteration plays a role in the pathogenesis of both glioblastoma subtypes. MET gain was also common in diffuse astrocytomas (38%), but less frequent in oligodendrogliomas (16%). MET gain in diffuse astrocytomas was associated with shorter survival (median, 43.0 vs. 70.7 months; P = 0.004), suggesting that MET gain is a useful prognostic marker for diffuse astrocytomas.

Figure 1

Quantitative PCR showing MET gain in low‐grade diffuse gliomas. The left‐hand figure shows the original quantitative PCR graph for low‐grade diffuse gliomas with (+MET gain) and without (−MET gain) MET gain. Relative CT values for MET and beta‐globin at different concentrations of normal control DNA are shown. The slopes of the curves are similar, suggesting equal efficiencies of the two PCR reactions (right).

Figure 2

Cumulative survival of patients with diffuse astrocytoma is significantly shorter for tumors with MET gain than for tumors without MET gain (median overall survival, 43.0 months vs. 70.7 months; P = 0.004). There was no significant difference in patient survival for glioblastomas with or without MET gain.