Investigating chromosome damage using fluorescent in situ hybridization to identify biomarkers of radiosensitivity in prostate cancer patients

Int J Radiat Biol. 2013 Dec;89(12):1087-93. doi: 10.3109/09553002.2013.825060. Epub 2013 Aug 15.

Abstract

Purpose: In order to evaluate fluorescent in situ hybridization (FISH) as a method for predicting radiosensitivity, this study examined the incidence of translocations, after exposure to in vitro radiation, in both normally responding patients and those exhibiting severe late effects after radiotherapy treatment.

Materials and methods: Patients were selected from a randomized trial for intermediate-risk prostate cancer. Of the patients entered on trial with mature follow-up, 3% developed grade 3 late proctitis. Blood samples were taken from this radiosensitive cohort along with matched control patients with no late proctitis. Whole blood samples were exposed to 0 or 4 Gy and cultured according to the International Atomic Energy Agency (IAEA) recommended methods. Colour junctions were evaluated in the resulting metaphases and scored according to the Protocol for Aberration Identification and Nomenclature Terminology (PAINT) system.

Results: Both groups were statistically similar at 0 Gy. After 4 Gy in vitro radiation, the radiosensitive group had significantly higher rates of chromosome damage in the number of colour junctions per cell (p = 0.002), the number of deletions per cell (p = 0.01) and the number of dicentrics per cell (p = 0.005).

Conclusions: These results indicate that the analysis of translocations using FISH after in vitro irradiation correlates with clinical response to radiation. This cytogenetic assay should be considered as a potential predictor of radiosensitivity.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Chromosomes / radiation effects*
  • Cohort Studies
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Male
  • Middle Aged
  • Poisson Distribution
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / radiotherapy
  • Radiation Tolerance*
  • Radiotherapy / methods
  • Translocation, Genetic / radiation effects

Substances

  • Biomarkers, Tumor