Considerations for radiotherapy in Bloom Syndrome: A case series

W.V Vogel,J.H.A.M Kaanders,C.M.R Weemaes,S Takada,M Van Deuren,I Pico,C.J Dommering,M.H.D Schoenaker,S.S.V Henriët,M.A.A.P Willemsen,M Van Der Burg

doi:10.1016/j.ejmg.2021.104293

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.

Highlights

Bloom Syndrome (BS) was first described by David Bloom in 3 children with severe growth deficiency and a telangiectatic erythema tous rash on the face (Bloom, 1954)
BS is often mentioned among the other DNA repair syndromes Ataxia Telangiectasia (A-T), Fanconi Anemia and Nijmegen Breakage Syndrome, which are all characterized by early onset cancer and an immunodeficiency (Taylor et al, 2019)
At 48 years she was diagnosed with BS based on bi-allelic mutations in the BLM gene detected by whole exome sequencing

Summary

Introduction

Bloom Syndrome (BS) was first described by David Bloom in 3 children with severe growth deficiency and a telangiectatic erythema tous rash on the face (Bloom, 1954). The clinical spectrum currently includes a number of additional features such as type 2 diabetes, im munodeficiency, infertility, and most importantly, predisposition to early onset cancer in multiple different organ systems (Flanagan and Cunniff, 1993). The Bloom registry in New York collected clinical data on BS patients from all over the world, including 145 BS patients with a malignancy. In these patients a total of 226 malignancies were described and the majority (149 or 66%) were carcinomas (Flanagan and Cunniff, 1993) The most common solid tumor in BS is colorectal carcinoma, which occurs at a median age of 35 (range 16–49) years (Cunniff et al, 2017). Besides a similar pre disposition to malignancies, these other DNA repair syndromes are all

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