Molecular markers for the response to radiotherapy

1. Research group name/project:
Molecular markers for the response to radiotherapy

2. Group leader and some key members (incl. from other depts./inst.):
Heidi Lyng (scientist), Debbie H. Svendsrud (technical assistant), Ragnhild Sørum (student), Gunnar B. Kristensen (dept. of Gynecology, DNR), Odd T. Brustugen (dept. of Oncology, DNR).

3. Home address on the internet:
http://radium.no/stokke

4. Department/Institute:
Department of Biophysics.

4b. Hospital (HF):
Det norske radiumhospital HF

5. Main aim of research group:
Our aims are to investigate the molecular parameters involved in cell cycle arrest, DNA repair, and cell death in tumor tissue during and after radiation treatment and to find possible relationships between molecular parameters and outcome of the radiation treatment.

6. Some important recent results (with a few key references):
Eighty patients are included at present. Two to four biopsies have been taken from each tumor both before start of the treatment and after a week of radiation treatment (10 Gy). Analysis by CGH of the pre-treatment samples has revealed extensive intratumor chromosomal heterogeneity, indicating how carcinoma progression and development of treatrment resistant clones occur (in press). Studies of the changes in gene expression after treatment are ongoing. Several of the genes that are regulated after radiation are known to be involved in the regulation of the cell cycle and apoptosis, e.g. MDM2, CDKN1A, and caspases, but the function of most of them is not known. The changes in gene and protein expression will be related to the genetic aberrations in the tumor, as well as to induction of cell cycle arrest and apoptosis. Eventually, all these data will be analyzed for prognostic value concerning treatment response and patient survival.

7. Methods in current use:
cDNA microarray, flow cytometry, fluorescent in situ hybridization, comparative genomic hybridization, PCR.

8. Available equipment:
Flow cytometers, fluorescence microscopes, PCR machines.

9. Collaborators:
9.1. Among Helse Sør hospitals : Paula DeAngelis (RH)
9.2. Other Norwegian collaborators: Ingrid K. Glad, Dept. of Mathematics, University of OsloArnoldo Frigessi, Dept.of Medical Statistics, University of Oslo
9.3. Collaborators from other countries: Mark van de Wiel, Eindhoven University of Technology, The Netherlands.

10. Some key search words:
cervical carcinoma, radiation response, genetic aberrations, gene expression, molecular and cellular phenotypes