[Genetics and brain gliomas].
Chromosome arms 1p and 19q codeletion, corresponding to an unbalanced reciprocal translocation t(1;19)(q10;p10), is seen in oligodendroglial tumours and is associated with better prognosis and better chemosensitivity. BRAF abnormalities are observed in pilocytic astrocytomas (tandem duplication-rearrangement) and in pleomorphic xanthoastrocytomas (BRAF V600E mutation). The vast majority of primary or de novo glioblastomas exhibit genetic abnormalities disrupting the intracellular signaling pathways of: transmembrane tyrosine kinase receptors to growth factors and their downstream signaling pathways (i.e. NF1-RAS-RAF-MAPK and PTEN-PI3K-AKT-TSC-mTOR); RB and; TP53. IDH1 and IDH2 mutations are frequent in diffuse grade II and grade III gliomas and in secondary glioblastomas. They are diagnostic and favorable independent prognostic biomarkers. In contrast, they are rare in primary or de novo glioblastomas and not reported in pilocytic astrocytomas. Germlin mutations in MSH2/MLH1/PMS2/MSH6, CDKN2A, TSC1/TSC2, PTEN, TP53 and NF1/NF2 predispose to glial tumors in the setting of hereditary cancer predisposition syndromes. Single nucleotide polymorphisms in TERT,CCDC26, CDKN2A/CDKN2B, RTEL, EGFR and PHLDB1 confer an inherited susceptibility to glial tumors.
AP-HP, groupe hospitalier Pitié-Salpêtrière, service de neurologie 2, Mazarin, 75651 Paris cedex 13, France.
Agusti
A
Alentorn
Marianne
M
Labussière
Marc
M
Sanson
Jean-Yves
JY
Delattre
Khê
K
Hoang-Xuan
Ahmed
A
Idbaih
D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D009837:Oligodendroglioma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics; D014178:Translocation, Genetic
D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins