Radiation‐induced genomic instability in breast carcinomas of the Swedish hemangioma cohort |
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Authors: | Jana Biermann,Britta Langen,Szil rd Nemes,Erik Holmberg,Toshima Z. Parris,Elisabeth Werner R nnerman,Hanna Engqvist,Anik Kov cs,Khalil Helou,Per Karlsson |
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Affiliation: | Jana Biermann,Britta Langen,Szilárd Nemes,Erik Holmberg,Toshima Z. Parris,Elisabeth Werner Rönnerman,Hanna Engqvist,Anikó Kovács,Khalil Helou,Per Karlsson |
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Abstract: | 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 hemangioma cohort that was treated with radium‐226 for skin hemangioma 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 in the tumor genome and thus a more unstable genome. Hence, the observed dose‐dependent GI in the tumor 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 hemangioma 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. |
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Keywords: | breast irradiation cancer genome instability long‐term radiation effects radiation‐induced genomic instability Swedish hemangioma cohort |
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