少图角质细胞瘤基因分型课件.pptVIP

16-10-2001 Genotyping of oligodendroglial tumors Prof.dr. Johan M. Kros, neuropathologist Erasmus Medical Center, Rotterdam, The Netherlands TP53 mutations in glial tumors From: P.C. Burger, Brain Pathology vol 12(2), 2002 Glioblastoma with oligodendroglial component Many unanswered questions The gene or genes on 1p Other genes associated with loss of 1p Is there a relation between loss of 1p and MGMT-silencing by hypermethylation of its promoter? Genetic heterogeneity and its relevance for clinical practice prog OD OD A OA intermediate OA OD OD OD OD A A A A OA OA OA OA OA OA OA OD OD OD OD A A A A OA OA OA OA OA A OD OD A What is “mixed”? Jeuken et al, J Pathol 194:81-7, 2001 Genomic heterogeneity revealed by CGH 1p 19q 10 + 7 1p 19q 10 + 7 1p 19q 10 + 7 or 1p 19q 1p 19q 10 + 7 low-grade astrocytoma anaplastic astrocytoma EGFR amplification (40%) and overexpression (60%) MDM2 amplification ( 10%) and overexpression (50%) P16 deletion (35%) LOH 10p and 10q PTEN mutation P53 mutation RB alteration TP53 mutation (65%) PDGF-A, PDGFR-? overexpression (60%) LOH 19q (50%) RB alteration (25%) LOH 10q PTEN mutation (5%) DCC loss of expression (50%) PDGFR-? amplification (10%) loss chrom. 10 19q loss 1p loss oligodendroglioma oligoastrocytoma “tertiary (?)” glioblastoma low-grade precursor lesion “secondary” glioblastoma “primary” glioblastoma He J. et al, J. Neuropathol. Exp. Neurol. 60, 863-71, 2001 Kraus J. et al, Acta Neuropathol. 101, 311-20, 2001 GBM with oligodendroglioma phenotypical characteristics carry a better prognosis and often show loss of 1p/19q Some recent developments in detection of clinically relevant genetic aberrations Multiplex Ligation-dependent Probe Amplification (MLPA): a method to investigate various deletions / amplifications in one assay – on paraffin-embedded material Chamberlaine et al., 1988; Beggs et al., 1990 In 18/19 oligodendrogliomas MLPA and FISH were concordant for presence or absence of