Читать книгу Intracranial Gliomas Part II - Adjuvant Therapy - Группа авторов - Страница 36

TCGA project identified four robust gene expression-based molecular subtypes of GBM, namely proneural, neural, classical, and mesenchymal [76]. Proneural tumors are associated with better outcome, mainly diagnosed in young adults, usually “secondary,” and typically characterized by mutations of IDH1/IDH2 and TP53. On the other hand, mesenchymal GBM carries the worst prognosis, usually presents in the elderly, and typically demonstrates PTEN loss and EGFR amplification [76]. Moreover, analysis of 272 GBM samples within TCGA project revealed a distinct subset of tumors with highly concordant DNA promoter hypermethylation within the CpG island, which was denoted as G-CIMP [29]. These tumors made up 8.8% of all investigated cases, and most (87.5%) belonged to the proneural subgroup, representing 30% of them. G-CIMP were mainly encountered in younger patients (median age 36 years), were associated with significantly better survival, and frequently had mutations of IDH1[29].

In fact, nearly all tumors with IDH1/IDH2 mutations exhibit G-CIMP due to the effects of D-2-hydroxyglutarate on DNA methylation [12]. In concordance, the vast majority of such neoplasms carry methylated MGMT promoter [77]. The incidence of G-CIMP is approximately 10 times greater in WHO grade II gliomas as compared with GBM, whereas WHO grade III tumors have an intermediate position [29]. In lower-grade gliomas this profile was noted twice as common in oligodendroglial (93%) than in astrocytic (45%) neoplasms [29]. More specifically, it is most typical for “classic” OD/AOD with 1p/19q co-deletion and for astrocytomas carrying mutations of TP53 and ATRX. Therefore, it has been suggested that tumors with the G-CIMP profile may be further subclassified with regard to the presence of such molecular alterations [7]. In WHO grade II and III gliomas G-CIMP is also associated with better survival of patients [29].