1. Considerations for radiotherapy in Bloom Syndrome
- Author
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M.E.L. van der Burg, C.J. Dommering, J.H.A.M. Kaanders, I. Pico, M. van Deuren, M.H.D. Schoenaker, Stefanie S. V. Henriet, Corry M.R. Weemaes, W.V. Vogel, Sanami Takada, Michèl A.A.P. Willemsen, Human genetics, and CCA - Cancer biology and immunology
- Subjects
Adult ,Male ,DNA repair ,medicine.medical_treatment ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Radiation Tolerance ,All institutes and research themes of the Radboud University Medical Center ,Genetics ,medicine ,Humans ,Bloom syndrome ,DNA Breaks, Double-Stranded ,Radiosensitivity ,Genetics (clinical) ,Immunodeficiency ,Cells, Cultured ,Chemotherapy ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,RecQ Helicases ,Radiotherapy ,Toxicity ,business.industry ,Carcinoma ,General Medicine ,Fibroblasts ,Middle Aged ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,medicine.disease ,Radiation therapy ,Ataxia-telangiectasia ,Chromosomal instability disorder ,Cancer research ,Female ,business ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Bloom Syndrome (BS) is a genetic DNA repair disorder, caused by mutations in the BLM gene. The clinical phenotype includes growth retardation, immunodeficiency and a strong predisposition to different types of malignancies. Treatment of malignancies in BS patients with radiotherapy or chemotherapy is believed to be associated with increased toxicity, but clinical and laboratory data are lacking. We collected clinical data of two Dutch BS patients with solid tumors. Both were treated with radiotherapy before the diagnosis BS was made and tolerated this treatment well. In addition, we collected fibroblasts from BS patients to perform in vitro clonogenic survival assays to determine radiosensitivity. BS fibroblasts showed less radiosensitivity than the severely radiosensitive Artemis fibroblasts. Moreover, studies of double strand break kinetics by counting 53BP1 foci after irradiation showed similar patterns compared to healthy controls. In combination, the clinical cases and laboratory experiments are valuable information in the discussion whether radiotherapy is absolutely contraindicated in BS, which is the Case in other DNA repair syndromes like Ataxia Telangiectasia and Artemis.
- Published
- 2021