BACKGROUND:  Ataxia-telangiectasia (A-T) is an inheritable neurological disorder resulting in a broad range of conditions beginning in childhood, progressing to the inability to walk during the teenage years, and death by the time the patient reaches his or her early 20s. Because A-T is caused by a recessive mutation in the ATM gene, only homozygotes suffer from these severe symptoms. Heterozygotes, although symptom-free, do possess an estimated 100-fold increase in susceptibility to cancer, particularly breast cancer, as well as an increased sensitivity to radiation. Because this correlation applies to cancer incidence, an interest in the expression of the ATM gene has resulted in the medical community. Present testing takes approximately 12 weeks and costs $1,400 for immunoblotting/colony survival assay or $2,000 for ATM gene sequencing. However, to date, there is no rapid, simple test that reliably identifies ATM heterozygotes.

INNOVATION:  Researchers at UCLA have identified a rapid assay to identify ATM gene carriers that would replace or function as a prescreening tool for other more expensive and time-consuming tests. This novel test uses peripheral blood mononuclear cells (PBMC) isolated from the blood of the patient. A portion of these cells are subjected to DNA damaging reagents, while another portion is left undamaged. The cells are then fixed in a manner that allows appropriate antibodies to enter the nuclei, enabling the determination of whether ATM kinase activity, which is absent from cells of patients with the ATM gene, is present. As one of the antibodies utilized is fluorescence tagged, the amount of fluorescence in the damaged and undamaged cells can be measured by flow cytometry. By comparing these fluorescence measurements to controls, the test can identify whether the subject is an ATM gene carrier. The entire test can be completed in half of a day, requires less than 2 million cells, and costs approximately $400.

POTENTIAL APPLICATIONS 

• Cancer and radiation susceptibility testing (identification of ATM gene carriers)
• A-T diagnosis

ADVANTAGES

• Less blood required than previous methods
• Significantly lower cost
• Less than one day of laboratory work required to obtain results

DEVELOPMENT-TO-DATE:  Testing was performed first on individuals with various DNA repair disorders, and then on 23 healthy controls, 11 obligate heterozygotes (the parents of affected children), and 6 patients with A-T. The test successfully differentiated between ATM gene carriers and non-carriers.

Reference: UCLA Case No. 2008-615