title: Increased chromosomal instability in peripheral lymphocytes and risk of human gliomas.
abstract: Brain tumors exhibit considerable chromosome instability (CIN), suggesting that genetic susceptibility may contribute to brain tumorigenesis. To test this hypothesis, in this pilot study, we examined for CIN in short-term lymphocyte cultures from 25 adult glioma patients and 28 age-, sex- and ethnicity-matched healthy controls (all Caucasian). We evaluated CIN by a multicolor fluorescence in situ hybridization assay using two probes: a classic satellite probe for a large heterochromatin breakage-prone region of chromosome 1 and an alpha satellite probe for a smaller region adjacent to the heterochromatin probe. Our results showed a significant increase in the mean number of spontaneous breaks per 1000 cells in glioma patients (mean +/- SD, 2.4+/-0.8) compared with controls (1.4+/-0.9; P < 0.001). By using the median number of breaks per 1000 cells in the controls as the cutoff value, we observed a crude odds ratio (OR) of 8.5 [95% confidence interval (CI) = 2.05-34.9, P < 0.001] for spontaneous breaks and brain tumor risk. After adjustment for age, sex and smoking status, the adjusted OR was 15.3 (95% CI, 2.71-87.8). A significant increase in cells with chromosome 1 aneuploidy (in the form of hyperdiploidy) (P < 0.001) was also observed in the glioma cases, with an adjusted OR of 6.6 (95% CI = 1.5-30, P < 0.05). These findings suggest that CIN can be detected in the peripheral blood lymphocytes of brain tumor patients and may be a marker for identifying individuals at risk.
authors.affiliation: Department of Epidemiology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: El-Zein
authors.forename: M L
authors.initials: ML
authors.lastname: Bondy
authors.forename: L E
authors.initials: LE
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: de Andrade
authors.forename: A J
authors.initials: AJ
authors.lastname: Sigurdson
authors.forename: J M
authors.initials: JM
authors.lastname: Bruner
authors.forename: A P
authors.initials: AP
authors.lastname: Kyritsis
authors.forename: V A
authors.initials: VA
authors.lastname: Levin
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000782:Aneuploidy; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D005910:Glioma / Q000097:blood / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors