title: Intratumoral patterns of clonal evolution in gliomas.
abstract: Few studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N = 16 probes) interphase-FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed >or=2 tumor cell clones, with higher numbers among high- versus low-grade gliomas (p = 0.001). Nine different cytogenetic patterns were found in the ancestral tumor clones. In most gliomas, ancestral clones showed abnormalities of chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition of additional abnormalities followed by tetraploidization. Conversely, early tetraploidization was associated with low-grade astrocytomas-2/3 pilocytic and 3/6 grade II diffuse astrocytomas-and combined loss of 1p36/19q13 with oligodendrogliomas, respectively; both aberrations were associated with a better patient outcome (p = 0.03). Overall, our results support the existence of different pathways of intratumoral evolution in gliomas.
authors.affiliation: Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Vital
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Tabernero
authors.forename: Inês
authors.initials: I
authors.lastname: Crespo
authors.forename: Olinda
authors.initials: O
authors.lastname: Rebelo
authors.forename: Hermínio
authors.initials: H
authors.lastname: Tão
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomes
authors.forename: Maria Celeste
authors.initials: MC
authors.lastname: Lopes
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D005910:Glioma / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D055815:Young Adult