TY - JOUR
T1 - Risk assessment for developing gliomas
T2 - A comparison of two cytogenetic approaches
AU - El-Zein, Randa
AU - Bondy, Melissa L.
AU - Wang, Li E.
AU - De Andrade, Mariza
AU - Sigurdson, Alice J.
AU - Bruner, Janet M.
AU - Kyritsis, Athanassios P.
AU - Levin, Victor A.
AU - Wei, Qingyi
N1 - Funding Information:
We thank Maureen Goode (Department of Scientific Publications) for editing the manuscript, and Joanne Sider and Joyce Brown for assistance in preparing the manuscript. This study was supported in part by National Cancer Institute grants CA 70334 and CA 74851 (to Q.W.), CA 70917 (to M.L.B.) and CA 55261 (to V.A.L.).
PY - 2001/1/25
Y1 - 2001/1/25
N2 - 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.
AB - 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.
KW - Brain tumors
KW - Fluorescence in situ hybridization
KW - Peripheral blood lymphocytes
KW - Susceptibility
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U2 - 10.1016/S1383-5718(00)00154-6
DO - 10.1016/S1383-5718(00)00154-6
M3 - Article
C2 - 11152970
AN - SCOPUS:0035945719
SN - 1383-5718
VL - 490
SP - 35
EP - 44
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1
ER -