Читать книгу Intracranial Gliomas Part II - Adjuvant Therapy - Группа авторов - Страница 22

Multiple genetic and cytogenetic alterations have been identified in gliomas and their number is constantly increasing. Nevertheless, the major abnormalities, which may carry important diagnostic, prognostic, and/or predictive information in cases of tumors in adults, include the following:

•Mutations of IDH1 and IDH2(located, respectively, at 2q33.3 and 15q26.1) typical for WHO grade II and III astrocytic and oligodendroglial tumors, and sGBM;

•Mutations of TP53 (located at 17p13.1) and ATRX (located at Xq21.1) typical for WHO grade II and III astrocytomas, and sGBM;

•1p/19q co-deletion along with mutations of CIC (protein capicua homolog; located at 19q13.2) and FUBP1(far upstream element-binding protein 1; located at 1p31.1) typical for WHO grade II and III oligodendroglial tumors with “classic” morphology;

•Mutations of TERT (telomerase reverse transcriptase; located at 5p15.33) promoter typical for IDH1/IDH2-mutant, 1p/19q co-deleted OD/AOD, and IDH wild-type GBM;

•Mutations or homozygous deletion (HD) of CDKN2A (cyclin-dependent kinase inhibitor 2A; located at 9p21), as well as loss of heterozygosity (LOH) of chromosome 9p, typical for HGG and playing an important role in malignant progression of both adult and pediatric gliomas, especially astrocytomas;

•Mutations or HD of PTEN (phosphatase and tensin homolog; located at 10q23.3), amplifications of EGFR (epidermal growth factor receptor; located at 7p12) and PDGFRA (platelet-derived growth factor receptor, alpha polypeptide; located at 4q12), as well as complete or partial LOH of chromosome 10 and gains of chromosome 7, typical for pGBM;

•Hypermethylation of MGMT (O⁶-methylguanine DNA methyltransferase; located at 10q26) promoter frequently encountered in diffusely infiltrating gliomas of all WHO grades, especially of those carrying the CpG (cytosine-phosphate-guanine) island methylator phenotype (G-CIMP) profile;

•Mutations or fusions of BRAF (B-isoform of rapidly accelerating fibrosarcoma; located at 7q34) typical for circumscribed astrocytomas, both in adults and children.