BACKGROUND AND PURPOSE: Ataxia Telangiectasia (A-T) heterozygotes constitute 0.36-1% of the general population. They have a higher risk of developing several types of cancer and may be more likely to suffer side-effects following radiotherapy than the general population. Their identification is both labor- and time-consuming and the sensitivity and specificity of the methods employed has not been evaluated. This paper describes a new approach to the identification of A-T heterozygotes based on a two-tier analysis of histone H2AX phosphorylation. MATERIALS AND METHODS: We compared the T-cell phenotype after exposure to 2Gy in nine obligate A-T heterozygotes and 17 normal donors. Examined end points were histone H2AX phosphorylation by flow cytometry 1h after irradiation (kinase proficiency) and the residual gamma-H2AX foci by confocal microscopy 72h after irradiation (DSB repair proficiency). RESULTS: The sequential use of these two methods results in 100% positive predictive value (PPV), 67% negative predictive value (NPV), 78% sensitivity, and 100% specificity. The overall hit rate, i.e. the ratio between the true positives plus the true negatives and the total number of observations was 85%. CONCLUSIONS: A-T heterozygotes can be identified by analysing irradiated T-cell H2AX phosphorylation level and residual gamma-H2AX foci.

Two-tier analysis of histone H2AX phosphorylation allows the identification of Ataxia Telangiectasia heterozygotes

TURINETTO, VALENTINA;ORLANDO, Luca;LANTELME, Erica Maria;BRUSCO, Alfredo;DE MARCHI, Mario;AMOROSO, Antonio;RICARDI, Umberto;GREGORI, Dario;GIACHINO, Claudia
2009-01-01

Abstract

BACKGROUND AND PURPOSE: Ataxia Telangiectasia (A-T) heterozygotes constitute 0.36-1% of the general population. They have a higher risk of developing several types of cancer and may be more likely to suffer side-effects following radiotherapy than the general population. Their identification is both labor- and time-consuming and the sensitivity and specificity of the methods employed has not been evaluated. This paper describes a new approach to the identification of A-T heterozygotes based on a two-tier analysis of histone H2AX phosphorylation. MATERIALS AND METHODS: We compared the T-cell phenotype after exposure to 2Gy in nine obligate A-T heterozygotes and 17 normal donors. Examined end points were histone H2AX phosphorylation by flow cytometry 1h after irradiation (kinase proficiency) and the residual gamma-H2AX foci by confocal microscopy 72h after irradiation (DSB repair proficiency). RESULTS: The sequential use of these two methods results in 100% positive predictive value (PPV), 67% negative predictive value (NPV), 78% sensitivity, and 100% specificity. The overall hit rate, i.e. the ratio between the true positives plus the true negatives and the total number of observations was 85%. CONCLUSIONS: A-T heterozygotes can be identified by analysing irradiated T-cell H2AX phosphorylation level and residual gamma-H2AX foci.
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http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TBY-4VFBX3R-1-4&_cdi=5155&_user=525216&_orig=search&_coverDate=07%2F31%2F2009&_sk=999079998&view=c&wchp=dGLzVlz-zSkWA&md5=9616ad4767c86e700ffb598016d92d23&ie=/sdarticle.pdf
ATM; Heterozygote; Histone H2AX; Ionising radiation
Porcedda P; Turinetto V; Orlando L; Lantelme E; Brusco A; De Marchi M; Amoroso A; Ricardi U; Gregori D; Giachino C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/56230
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