Journal Article

Increased chromosomal instability in peripheral lymphocytes and risk of human gliomas

Randa El-Zein, Melissa L. Bondy, Li-E Wang, Mariza de Andrade, Alice J. Sigurdson, Janet M. Bruner, Athanassios P. Kyritsis, Victor A. Levin and Qingyi Wei

in Carcinogenesis

Volume 20, issue 5, pages 811-815
Published in print May 1999 | ISSN: 0143-3334
Published online May 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.5.811
Increased chromosomal instability in peripheral lymphocytes and risk of human gliomas

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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.

Keywords: CI, confidence interval; CIN, chromosomal instability; FISH, fluorescencein situ hybridization; OR, odds ratio; PBD, phosphate-buffered detergent; SSC, standard saline citrate.

Journal Article.  4006 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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