Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas.
Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas. We have used fluorescent microsatellite markers to examine a series of 83 patients, 34 with anaplastic astrocytoma (grade 3) and 49 with glioblastoma multiforme (grade 4), for LOH of chromosome 10. Genotype analysis revealed LOH for all informative chromosome 10 markers in 12 (35%) of patients with grade 3 and 29 (59%) grade 4 tumours respectively, while partial LOH was found in a further eight (24%) grade 3 and ten (20%) grade 4 tumours. Partial LOH, was confined to the long arm (10q) in six and the short arm (10p) in three cases, while alleles from both arms were lost in four cases. Five tumours (one grade 3 and four grade 4) showed heterogeneity with respect to loss at different loci. There was a correlation between any chromosome 10 loss and poorer performance status at presentation (chi2 P = 0.005) and with increasing age at diagnosis (Mann-Whitney U-test P = 0.034) but not with tumour grade (chi2 p= 0.051). A Cox multivariate model for survival duration identified age (proportional hazards (PH), P= 0.004), grade (PH, P= 0.012) and any loss of chromosome 10 (PH, P= 0.009) as the only independent prognostic variables. Specifically, LOH for chromosome 10 was able to identify a subgroup of patients with grade 3 tumours who had a significantly shorter survival time. We conclude that LOH for chromosome 10 is an independent, adverse prognostic variable in high-grade glioma.
Balesaria
S
S
Department of Cancer Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, UK.
Brock
C
C
Bower
M
M
Clark
J
J
Nicholson
S K
SK
Lewis
P
P
de Sanctis
S
S
Evans
H
H
Peterson
D
D
Mendoza
N
N
Glaser
M G
MG
Newlands
E S
ES
Fisher
R A
RA
D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002879:Chromosomes, Human, Pair 10; D005910:Glioma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D011379:Prognosis; D016896:Treatment Outcome