Molecular radiobiology
Radiation-induced effects on gene expression: An in vivo study on breast cancer

https://doi.org/10.1016/j.radonc.2006.07.007Get rights and content

Abstract

Background and Purpose

Breast cancer is diagnosed worldwide in approximately one million women annually and radiation therapy is an integral part of treatment. The purpose of this study was to investigate the molecular basis underlying response to radiotherapy in breast cancer tissue.

Material and Methods

Tumour biopsies were sampled before radiation and after 10 treatments (of 2 Gray (Gy) each) from 19 patients with breast cancer receiving radiation therapy. Gene expression microarray analyses were performed to identify in vivo radiation-responsive genes in tumours from patients diagnosed with breast cancer. The mutation status of the TP53 gene was determined by using direct sequencing.

Results and conclusion

Several genes involved in cell cycle regulation and DNA repair were found to be significantly induced by radiation treatment. Mutations were found in the TP53 gene in 39% of the tumours and the gene expression profiles observed seemed to be influenced by the TP53 mutation status.

Section snippets

Patients

Patients with ulcerating breast cancer (stage III and IV) or local relapse from breast cancer were invited to participate in this study. Our Institutional Review Board and the Regional Ethical Committee approved the study and informed consent was signed by the patients included. Tumour tissue was biopsied before radiation and after 10 treatments (totally 20 Gy) and stored at −80 °C. The pathologist (JMN) evaluated the tumour content in the 21 biopsies with sufficient material, to assure that

Results

Samples were collected from 19 patients, and total RNA was successfully isolated from 19 of the tumours collected before radiotherapy and from 17 of the samples collected post-treatment. We did not get enough RNA for further analyses from two post-treatment samples (not evaluated by pathologist due to small biopsies). Clinical characteristics are shown in Table 1.

Unsupervised hierarchical clustering showed that the before- and after-samples from the same patient tended to cluster together (Fig.

Discussion

Breast cancer affects many women worldwide, and radiotherapy is an important part of the treatment. However, clinicians see a wide range of effects and side-effects, but the biology underlying tissue responses is not yet fully understood. We have performed expression microarray analyses and detected genes induced by the radiotherapy. DDB2 and CDKN1A were the genes most significantly induced. DDB2 is involved in DNA repair, is regulated by TP53, and transcriptionally activated by the tumour

Acknowledgement

This work was supported by grants from the Research Council of Norway, Lillemor Grobstoks Foundation and funding from The Norwegian Radium Hospital’s gifts.

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