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Radiation-induced genomic instability in breast carcinomas of the Swedish haemangioma cohort.

Journal article
Authors Jana Biermann
Britta Langen
Szilard Nemes
Erik Holmberg
Toshima Z Parris
Elisabeth Werner Rönnerman
Hanna Engqvist
Anikó Kovács
Khalil Helou
Per Karlsson
Published in Genes, chromosomes & cancer
Volume 58
Issue 9
Pages 627-35
ISSN 1098-2264
Publication year 2019
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Pages 627-35
Language en
Keywords Radiation-induced genomic instability; Swedish haemangioma cohort; breast irradiation; cancer genome instability; long-term radiation effects
Subject categories Cancer and Oncology, Bioinformatics (Computational Biology), Biological Sciences


Radiation-induced genomic instability (GI) is hypothesized to persist after exposure and ultimately promote carcinogenesis. Based on the absorbed dose to the breast, an increased risk of developing breast cancer was shown in the Swedish haemangioma cohort that was treated with radium-226 for skin haemangioma as infants. Here, we screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess GI and chromothripsis-like patterns associated with the absorbed dose to the breast. Higher absorbed doses were associated with increased numbers of copy number alterations (CNAs) in the tumour genome and thus a more unstable genome. Hence, the observed dose-dependent GI in the tumour genome is a measurable manifestation of the long-term effects of irradiation. We developed a highly predictive Cox regression model for overall survival based on the interaction between absorbed dose and GI. The Swedish haemangioma cohort is a valuable cohort to investigate the biological relationship between absorbed dose and GI in irradiated humans. This work gives a biological basis for improved risk assessment to minimize carcinogenesis as a secondary disease after radiation therapy. This article is protected by copyright. All rights reserved.

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