BACKGROUND AND PURPOSE: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. MATERIALS AND METHODS: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. RESULTS: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0Gy), irradiated (4Gy) or radiation response (4-0Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. CONCLUSIONS: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.
BACKGROUND AND PURPOSE: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. MATERIALS AND METHODS: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. RESULTS: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0Gy), irradiated (4Gy) or radiation response (4-0Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. CONCLUSIONS: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.
Authors: Pavel Lobachevsky; Trevor Leong; Patricia Daly; Jai Smith; Nickala Best; Jonathan Tomaszewski; Ella R Thompson; Na Li; Ian G Campbell; Roger F Martin; Olga A Martin Journal: Cancer Lett Date: 2016-09-28 Impact factor: 8.679
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Authors: Carsten Herskind; Christopher J Talbot; Sarah L Kerns; Marlon R Veldwijk; Barry S Rosenstein; Catharine M L West Journal: Cancer Lett Date: 2016-03-02 Impact factor: 8.679
Authors: Jan Baijer; Nathalie Déchamps; Hervé Perdry; Pablo Morales; Sarah Kerns; Alexandre Vasilescu; Sylvain Baulande; David Azria; Paul Henri Roméo; Annette Schmitz Journal: Oncotarget Date: 2016-04-19
Authors: Mohammad Habash; Luis C Bohorquez; Elizabeth Kyriakou; Tomas Kron; Olga A Martin; Benjamin J Blyth Journal: Cancers (Basel) Date: 2017-10-27 Impact factor: 6.639