Intratumoral patterns of clonal evolution in gliomas.
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.
Vital
Ana Luísa
AL
Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Tabernero
Maria Dolores
MD
Crespo
Inês
I
Rebelo
Olinda
O
Tão
Hermínio
H
Gomes
Fernando
F
Lopes
Maria Celeste
MC
Orfao
Alberto
A
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