biostudies-literatureLobachevsky PPeter MacCallum Cancer FoundationIntramural NIH HHSNational Cancer Institute, National Institutes of Health, USA212-219https://www.ebi.ac.uk/biostudies/studies/S-EPMC5159273biostudies-literatureUnknown383(2)A small percentage of cancer radiotherapy patients develop abnormally severe side effects as a consequence of intrinsic radiosensitivity. We analysed the γ-H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and plucked eyebrow hair follicles from 16 patients who developed severe late radiation toxicity following radiotherapy, and 12 matched control patients. Longer retention of the γ-H2AX signal and lower colocalization efficiency of repair factors in over-responding patients confirmed that DNA repair in these individuals was compromised. Five of the radiosensitive patients harboured LoF mutations in DNA repair genes. An extensive range of quantitative parameters of the γ-H2AX response were studied with the objective to establish a predictor for radiosensitivity staCancer lettersCompromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity.PMC51592731343Z01 BC006140Leong TTomaszewski JMartin RFBest NDaly PThompson ERMartin OASmith JLobachevsky PLi NCampbell IGfalseCompromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity.A small percentage of cancer radiotherapy patients develop abnormally severe side effects as a consequence of intrinsic radiosensitivity. We analysed the γ-H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and plucked eyebrow hair follicles from 16 patients who developed severe late radiation toxicity following radiotherapy, and 12 matched control patients. Longer retention of the γ-H2AX signal and lower colocalization efficiency of repair factors in over-responding patients confirmed that DNA repair in these individuals was compromised. Five of the radiosensitive patients harboured LoF mutations in DNA repair genes. An extensive range of quantitative parameters of the γ-H2AX response were studied with the objective to establish a predictor for radiosensitivity sta2016-01-01T00:00:00Z2016 Dec2026-05-04T13:26:57.017Z2019-03-27T02:31:37ZS-EPMC51592732769345710.1016/j.canlet.2016.09.010