Risk assessment for developing gliomas

A comparison of two cytogenetic approaches

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume490
Issue number1
DOIs
StatePublished - Jan 25 2001
Externally publishedYes

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Chromosomal Instability
Fluorescence In Situ Hybridization
Glioma
Cytogenetics
Mutagens
Odds Ratio
Lymphocytes
Chromatids
Polyploidy
Tumor Biomarkers
Chromosome Aberrations
Sensitivity and Specificity

Keywords

  • Brain tumors
  • Fluorescence in situ hybridization
  • Peripheral blood lymphocytes
  • Susceptibility

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Risk assessment for developing gliomas : A comparison of two cytogenetic approaches. / El-Zein, Randa; Bondy, Melissa L.; Wang, Li E.; De Andrade, Mariza; Sigurdson, Alice J.; Bruner, Janet M.; Kyritsis, Athanassios P.; Levin, Victor A.; Wei, Qingyi.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 490, No. 1, 25.01.2001, p. 35-44.

Research output: Contribution to journalArticle

El-Zein, Randa ; Bondy, Melissa L. ; Wang, Li E. ; De Andrade, Mariza ; Sigurdson, Alice J. ; Bruner, Janet M. ; Kyritsis, Athanassios P. ; Levin, Victor A. ; Wei, Qingyi. / Risk assessment for developing gliomas : A comparison of two cytogenetic approaches. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2001 ; Vol. 490, No. 1. pp. 35-44.
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abstract = "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.",
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T2 - A comparison of two cytogenetic approaches

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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

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