Molecular radiobiologyRadiation-induced effects on gene expression: An in vivo study on breast cancer
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.
References (20)
- et al.
Functional genomics as a window on radiation stress signalling
Oncogene
(2003) - et al.
Human in vivo radiation-induced biomarkers: gene expression changes in radiotherapy patients
Cancer Res
(2004) - et al.
DNA damage activates ATM through intermolecular autophosphorylation and dimmer dissociation
Nature
(2003) - et al.
The Stanford Microarray Database accommodates additional microarray platforms and data formats
Nucleic Acids Res
(2005) TP53 and breast Cancer
Hum Mutat
(2003)- et al.
Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation
Oncogene
(2003) - et al.
Cluster analysis and display of genome-wide expression patterns
Proc Natl Acad Sci USA
(1998) - et al.
P53 and radiation responses
Oncogene
(2003) Cancer.p53, guardian of the genome
Nature
(1992)- et al.
The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer
Clin Cancer Res
(2006)
Cited by (21)
Response to Preoperative Radiation Therapy in Relation to Gene Expression Patterns in Breast Cancer Patients
2020, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :In addition to the inflammatory response, significant changes in gene expression of genes involved in programmed cell death were observed in both studies. In concordance with our results, expression of several genes involved in cell cycle regulation and DNA repair were significantly induced by radiation in 19 patients with locally advanced or relapsed breast cancer.32 Similar deregulation of processes has been described after RT in cell lines of low-grade breast cancer.33
Predictive Factors for Local Recurrence in Breast Cancer
2012, Seminars in Radiation OncologyCitation Excerpt :However, in 2 large studies, radiation sensitivity of skin fibroblasts has not been confirmed as predictive for breast fibrosis after RT.61,62 In a study by Helland et al,63 tumor material of 19 breast cancer patients was investigated to study the molecular basis underlying response to RT. Tumor biopsies were sampled before radiation and after 10 treatments of 2 Gy.
DNA methylation changes in cells regrowing after fractioned ionizing radiation
2011, Radiotherapy and OncologyCitation Excerpt :We suggested that these differences result from altered DNA methylation, as described for repeated exposures to other agents, e.g. cisplatin [7]. In fact, our cells reacted to the treatment on the transcriptional level, as measured by a significant upregulation of CDKN1A mRNA, a classical radiation-marker [22,23], 48 h after FIR (data not shown). However, the genome-wide MCIp screen for differentially methylated CpG islands revealed only minor FIR-induced changes.
Using Microarray Analysis as a Prognostic and Predictive Tool in Oncology: Focus on Breast Cancer and Normal Tissue Toxicity
2008, Seminars in Radiation OncologyCitation Excerpt :It should be noted that these are studies with a small sample size and that proper validation is lacking. In 19 locally advanced breast cancer patients, Helland et al15 analyzed gene expression profiles in biopsies during a course of radiation treatment (after 20 Gy; 10 fractions of 2 Gy) and compared these with those in baseline biopsies and validated results using reverse-transcription polymerase chain reaction. They did not have data on clinical tumor response but focused on changes in gene expression during treatment.
Translational research in radiotherapy - Getting closer to the bedside
2007, Radiotherapy and Oncology