Deletion and 1p/19q codeletion were respectively 65.4 and 63.3 in oligodendrogliomas, 28.7 and 21.6

Deletion and 1p/19q codeletion were respectively 65.4 and 63.3 in oligodendrogliomas, 28.7 and 21.6 in oligoastrocytomas, 13.2 and 7.5 in astrocytomas, 11.6 and 2.9 in glioblastomas [30]. Established indicators of the favorable outcome of oligodendroglial tumors include LOH on chromosomes 1p and 19q, which may indicate a loss of function of as yet unknown tumor-suppressor genes located in those regions [31]. LOH of 1p in the heterogeneous population of malignant gliomas may be one of the vital factors besides MGMT promoter methylation that predict better outcome in patients treated with TMZ [32].Yan et al. Journal of Experimental Clinical Cancer Research 2011, 30:58 http://www.jeccr.com/content/30/1/Page 3 ofMutations in IDH1/2 are a common feature of a major subset of primary human brain tumors [33]. Recent studies reported that mutations usually affected amino acid 132 of IDH1 in more than 70 of grade IIIII gliomas and secondary glioblastomas. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid (R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28854080 had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild-type IDH genes [34,35]. IDH1 mutation contributes to tumorigenesis partly through induction of the HIF-1 pathway [36]. And it has been recently reported that tumor-derived IDH1 and IDH2 mutations reduced aKG and accumulated a a-KG antagonist, 2-hydroxyglutarate (2-HG), leading to genome-wide histone and DNA methylation alterations [37]. 2-HG accumulation caused by IDH mutation was also reported to be involved in the RG7800 mechanism of action formation of malignant gliomas [38]. A recent study has demonstrated that IDH mutation was correlated with a higher rate of response to temozolomide and appeared to be a significant marker of positive prognosis in low-grade gliomas [39]. Taken together, mutations in IDH genes seem to arise from a common glial precursor and play an important role in the formation of specific glioma subtype in which IDH1/2 mutation functions as oncogene addiction. MicroRNAs (miRNAs) belong to a recently discovered class of small non-coding RNA molecules that regulate the expression of multiple target genes. Some miRNAs, referred to as oncomiRs, show differential expression levels in cancer and are able to affect cellular transformation, carcinogenesis and metastasis, acting either as oncogenes or tumour suppressors. Oncogene addiction to oncomiRs has been proposed in several human cancers [19,40,41]. A lot of studied showed that the aberrant expression miRNAs, including miR-21, miR-221/222, miR-181s and miR-34s, played an important role in gliomagenesis [42-45]. Overexpression of miR-21 could lead to a malignant phenotype, demonstrating that mir-21 was a genuine oncogene. When miR-21 was inactivated, the tumours regressed completely in a few days, partly as a result of apoptosis [42]. And miR-181a and 181b functioned as tumor suppressors in glioma cells [44]. These results demonstrate that tumors could become addicted to oncomiRs and support efforts in treating human cancers through pharmacological inactivation of miRNAs such as miR-21 or upregulation of miR-181s.aberrations was identified in gliomas, only a subset of genes acting as drivers in carcinogenesis can be recognized as oncogene addition. Meanwhile, most genes just act as downstream effectors of addicted oncogenes. Oncogene addiction is an ideal potential target for.