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Expression of the ATM gene is significantly reduced in sporadic breast carcinomas
1Department of Neuropathology, University of Bonn Medical Center, Germany.
Abstract:
The gene mutated in ataxia telangiectasia (A-T) patients (ATM) is located on chromosome 11q22-23, a region frequently altered in mammary tumors. Patients homozygous for ATM mutations are prone to develop a variety of different neoplasms. Female heterozygotes have been reported to carry a 5- to 8-fold increased risk of breast cancer. However, germline mutations in the ATM gene are rare in women with sporadic breast carcinomas. Most of the alterations described in A-T patients result in a functionally inactive ATM protein. Moreover, it has been suggested that mutations of the ATM gene in A-T patients influence the amount of ATM mRNA and that this may affect the severity of the disease. In the present study, we have analyzed ATM transcripts in a series of 39 breast carcinomas, 14 benign breast lesions and 12 normal breast tissue samples. ATM mRNA levels were determined by semiquantitative competitive RT-PCR. Competitor RNA molecules for the ATM gene and the housekeeping gene beta-2-microglobulin (B2M) were generated by PCR mutagenesis. Low concentrations of ATM transcripts were detected in breast carcinomas, intermediate levels in benign lesions and highest levels in normal breast tissue specimens (F-test, p = 0.0013). Our results indicate that reduced expression of the ATM gene may contribute to the development and/or malignant progression of breast carcinomas.
Insights
Reduced expression of the ATM gene is linked to breast cancer development. ATM mRNA levels were significantly lower in breast carcinomas compared to normal tissue, suggesting a role in tumorigenesis.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The ATM gene, mutated in ataxia telangiectasia (A-T), is located on chromosome 11q22-23, a region implicated in mammary tumors.
- ATM mutations predispose A-T patients to various neoplasms, and female heterozygotes have an increased breast cancer risk.
- While germline ATM mutations are rare in sporadic breast cancer, alterations often lead to inactive ATM protein and may affect disease severity.
Purpose of the Study:
- To investigate the role of ATM gene expression in breast carcinogenesis.
- To quantify ATM mRNA levels in normal breast tissue, benign lesions, and malignant breast carcinomas.
Main Methods:
- Analysis of ATM transcripts in 39 breast carcinomas, 14 benign breast lesions, and 12 normal breast tissue samples.
- Quantification of ATM mRNA levels using semiquantitative competitive RT-PCR.
- Generation of competitor RNA for ATM and beta-2-microglobulin (B2M) via PCR mutagenesis.
Main Results:
- ATM mRNA levels were significantly lower in breast carcinomas compared to benign lesions and normal breast tissue (F-test, p = 0.0013).
- A clear gradient of decreasing ATM transcript concentration was observed from normal tissue to benign lesions to carcinomas.
- These findings suggest a correlation between reduced ATM expression and breast cancer.
Conclusions:
- Reduced expression of the ATM gene may play a role in the initiation and/or progression of breast carcinomas.
- ATM mRNA levels serve as a potential biomarker in breast tissue analysis.
- Further research is warranted to elucidate the precise mechanisms by which ATM downregulation contributes to breast cancer development.