The pro-proliferative function RG-7388 mouse of FUBP1 protein has been linked to both the transcriptional activation of the immediate-early gene MYC and the repression of the cell
cycle inhibitor gene p21 . We observed a significant association between FUBP1 protein expression and the proliferation index, which suggests that the FUBP1/MYC/p21 cell cycle regulatory axis is also functional in gliomas. In contrast, we demonstrated that in a subset of gliomas showing oligodendroglial differentiation the loss of FUBP1 was restricted to glioma cells and that intermingled residual neurones, reactive astrocytes, microglia or endothelial cells still displayed FUBP1 expression at various levels (Figure 4). The loss of FUBP1 protein expression significantly correlated with IDH1 mutation (R132H) and 1p/19 LOH, genetic aberrations that are both frequently found in gliomas with oligodendroglial differentiation (Table 2) [17,18]. A similar loss of protein expression in immunohistochemical analyses has recently been described for CIC, another molecule frequently mutated in tumours with oligodendroglial differentiation [1,4]. Especially the association between 1p LOH and low FUBP1 expression is interesting as FUBP1 is localized to chromosome 1p . The loss of 1p selleck chemicals llc might then reveal the masked effects of heterozygous genetic aberrations present on the remaining 1p
arm. To date, the reported FUBP1 mutations have been predicted to result in deletions or nonsense sequences. Therefore, Clomifene we hypothesized that the loss of FUBP1 protein expression observed by immunohistochemistry might not only be associated with 1p LOH, but also predict
the FUBP1 mutational status. Fifteen oligodendroglioma samples representing the full range of FUBP1 protein expression levels were submitted for mutational analysis of the FUBP1 exome. While no mutations were detected in the cases with moderate or strong FUBP1 protein expression, six functional FUBP1 mutations were discovered in patients with absent (n = 5) or very low (n = 1) FUBP1 protein expression levels in neoplastic oligodendroglioma cells. FUBP1 immunonegativity predicted FUBP1 mutation with a sensitivity of 100% and a specificity of 90%. These findings indicate that the analysis of FUBP1 expression by immunohistochemistry serves as a quick and inexpensive screening method for glioma patients, rather than using more expensive and time-consuming genetic sequencing of the 20 exon spanning FUBP1 gene. The fact that normal oligodendrocytes are also mainly FUBP1 negative may constitute a limitation of this potential diagnostic method. In summary, our findings show that in comparison with normal CNS tissue, FUBP1 expression levels are significantly increased in gliomas, independent of the subtype and WHO grade. In general, FUBP1 expression was associated with an increased proliferation index.