Risk assessment for developing gliomas: A comparison of two cytogenetic approaches

Chromosome instability (CIN) measured as chromosome aberrations has long been suggested as a cancer susceptibility biomarker. Conventional cytogenetic end-points are now being improved by combining molecular methods, which increases the sensitivity, specificity, and precision of the assay. In this study we examined both spontaneous and γ-ray induced CIN in lymphocyte cultures from 51 previously untreated glioma patients and 51 age-, sex- and ethnicity-matched controls. CIN was assessed using two parallel methods: (1) the mutagen sensitivity (MS) assay and (2) the multicolor fluorescence in situ hybridization (FISH) assay. The frequency of spontaneous breaks was significantly higher in glioma patients (mean ± S.D., 2.12 ± 1.07) than in controls (1.24 ± 0.86, P < 0.001) when using the FISH assay but not the MS assay (0.019 ± 0.02 and 0.019 ± 0.01, respectively; P = 0.915). Similarly, the frequency of induced chromatid breaks was significantly higher using the FISH assay (3.39 ± 1.72) but not the MS assay (0.42 ± 0.16) in the patients versus controls (2.08 ± 1.18 and 0.37 ± 0.15, respectively; P < 0.001 and P = 0.10, respectively). By using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (ORs) of 5.13 (95% CI = 2.23-12.1) for spontaneous and 4.86 (95% CI = 2.08-11.4) for induced CIN using the FISH assay, whereas the ORs were 1.32 (95% CI = 0.49-3.58) and 1.28 (95% CI = 0.59-2.80) for spontaneous and induced CIN using the MS assay. There was also a significant increase in the frequency of hyperdiploid cells in the glioma cases which could only be detected using the FISH assay (OR = 4.0, 95% CL = 0.9-17.0). By combining both methods an estimated risk of 7.0 (95% CI = 1.7-25.6) was observed. There was no correlation between the breaks detected by the two methods suggesting that each method is a measure of a different event. The results indicate that using the multicolor FISH assay for detection of CIN in peripheral blood lymphocytes in glioma patients is a more useful marker for risk assessment.