As many childhood gliomas are associated with activation of BRAF, we have explored the combination of ionizing radiation with MEK inhibition in a model of BRAF-mutant anaplastic astrocytoma.
When all of the data were combined and compared, 96% of GBs (87 of 91) and 88% of AAs (7 of 8) with abnormal G1-S transition control also had deregulated p53 pathway.
In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas.
Therefore, IDH mutation would be most useful when assessing prognosis of patients with grade 3 glioma with intact 1p/19q; anaplastic astrocytomas account for most of these grade 3 gliomas.
LOH on 9p and/or CDKN2A deletion occurred more often in glioblastomas (P < 0.001), LOH on 17p/TP53 mutations occurred more frequently in anaplastic astrocytomas (AAs; P = 0.112), and LOH on 10q/PTEN mutation frequency was similar in glioblastomas and AAs (P < 0.001).
To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV).
To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV).
No SSCP alterations were observed in any of the p53 fragments amplified from WHO grade I pilocytic astrocytomas and WHO grade III anaplastic astrocytomas.
Primary (de novo) glioblastomas develop in older patients and are characterized by epidermal growth factor (EGF) receptor amplification/overexpression, p16 deletion, and PTEN mutations, whereas secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma develop in younger patients and frequently contain p53 mutations.
Secondary glioblastomas that developed through progression from low-grade or anaplastic astrocytoma had TP53 mutations in 16 (84%) of 19 cases, but none contained mutations of the NBS1 gene.
Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age = 45 ± 14 years) and used to extract individual level, gray matter connectomes.
Diffuse astrocytoma (DA), anaplastic astrocytoma (AA), and glioblastoma (GBM) are defined by the World Health Organization (WHO) based on IDH-mutational status.
We examined TP53 status in relation to telomere maintenance mechanism (TMM) in 108 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma from New Zealand and United Kingdom.
Our study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients.
We evaluated nuclear cMYC protein levels and IDH1 (R132H) by immunohistochemistry in patients with oligodendroglioma/oligoastrocytomas (n = 20), astrocytomas (grade II) (n = 19), anaplastic astrocytomas (n = 21) or glioblastomas (n = 111).
We here report neuroimaging findings in a 69-year-old man with a "butterfly" pattern on dynamic FET [O-(2-[F]-fluoroethyl)-L-tyrosine] PET and the diagnosis of an anaplastic astrocytoma (WHO grade III; IDH-1/-2 wildtype, no 1p/19q co-deletion) but without typical MRI contrast enhancement.
Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively.
Loss of heterozygosity (LOH) was determined by Southern transfer analysis of somatic and tumor DNA from these same patients using polymorphic markers for various loci on chromosomes 10 and 17. p53 mutations were found in 7 of 25 glioblastomas (28%), in 5 of 14 anaplastic astrocytomas (36%) but in 0 of 6 low-grade astrocytomas. p53 mutations were found in 62% of patients with LOH on chromosome 17p.
Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma.