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World J Gastroenterol. May 21, 2007; 13(19): 2669-2674
Published online May 21, 2007. doi: 10.3748/wjg.v13.i19.2669
Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response
Jacqueline JCM Kruse, Fiona A Stewart
Jacqueline JCM Kruse, Fiona A Stewart, The Netherlands Cancer Institute, Division of Experimental Therapy (H6), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Fiona A Stewart, The Netherlands Cancer Institute, Department of Experimental Therapy (H6), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. f.stewart@nki.nl
Telephone: +31-20-5122036 Fax: +31-20-5122050
Received: December 15, 2006
Revised: December 30, 2006
Accepted: January 17, 2007
Published online: May 21, 2007
Abstract

Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research. The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PubMed literature search was conducted using the following keywords and combination of terms: radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways: (1) to generate gene signatures to identify sensitive and resistant populations (prognosis); (2) to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack (diagnosis); (3) to identify genes and pathways involved in tissue response to injury (mechanistic). In this article we will review all (relevant) papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

Keywords: Radiation; Normal tissue response; Microarrays; Gene expression; Limitations