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Low levels of ATM in breast cancer patients with clinical radiosensitivity

Zhiming Fang1, Sergei Kozlov2, Michael J McKay3, Rick Woods2, Geoff Birrell2, Carl N Sprung4, Dédée F Murrell5, Kiran Wangoo1, Linda Teng2, John H Kearsley1, Martin F Lavin2, Peter H Graham1 and Raymond A Clarke1*

Author Affiliations

1 Department of Radiation Oncology, St George Clinical School of Medicine University of NSW, St George Hospital, Kogarah, NSW 2217, Australia

2 Queensland Institute of Medical Research Herston, Queensland 4006, Australia

3 Australian National University and The Canberra Hospital Department of Radiation Oncology, Building 3, Level 1, Garran, A.C.T. Australia

4 Centre for Women's Health Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia

5 Department of Dermatology, St George Clinical School of Medicine University of NSW, St George Hospital, Kogarah, NSW 2217, Australia

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Genome Integrity 2010, 1:9 doi:10.1186/2041-9414-1-9

Published: 24 June 2010

Abstract

Background and Purpose

Adjuvant radiotherapy for cancer can result in severe adverse side effects for normal tissues. In this respect, individuals with anomalies of the ATM (ataxia telangiectasia) protein/gene are of particular interest as they may be at risk of both breast cancer and clinical radiosensitivity. The association of specific ATM gene mutations with these pathologies has been well documented, however, there is uncertainty regarding pathological thresholds for the ATM protein.

Results

Semi-quantitative immuno-blotting provided a reliable and reproducible method to compare levels of the ATM protein for a rare cohort of 20 cancer patients selected on the basis of their severe adverse normal tissue reactions to radiotherapy. We found that 4/12 (33%) of the breast cancer patients with severe adverse normal tissue reactions following radiotherapy had ATM protein levels < 55% compared to the mean for non-reactor controls.

Conclusions

ATM mutations are generally considered low risk alleles for breast cancer and clinical radiosensitivity. From results reported here we propose a tentative ATM protein threshold of ~55% for high-risk of clinical radiosensitivity for breast cancer patients.