Expression of the ATM gene is significantly reduced in sporadic breast carcinomas

• Published in: International journal of cancer Vol. 78; no. 3; pp. 306 - 309
• Main Authors: Waha, Andreas, Sturne, Chris, Kessler, Astrid, Koch, Anke, Kreyer, Ellen, Fimmers, Rolf, Wiestler, Otmar D., von Deimling, Andreas, Krebs, Dieter, Schmutzler, Rita K.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 29-10-1998; Wiley-Liss
• Subjects: Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Breast - metabolism; Breast Diseases - genetics; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cell Cycle Proteins; Chromosome Mapping; Chromosomes, Human, Pair 11; DNA Mutational Analysis; DNA Primers; DNA, Neoplasm - analysis; DNA-Binding Proteins; Female; Genetic Markers; Gynecology. Andrology. Obstetrics; Humans; Leucine Zippers; Loss of Heterozygosity; Mammary gland diseases; Medical sciences; Microsatellite Repeats; Neoplasm Invasiveness; Protein-Serine-Threonine Kinases; Proteins - genetics; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Transcription, Genetic; Tumor Suppressor Proteins; Tumors; Chromosomal aberration; Human; Carcinoma; Malignant tumor; Gene expression; Mammary gland diseases; Messenger RNA; Loss of heterozygosity; Cytogenetics; Deletion; Abnormal chromosome; Genetics; Mammary gland; Mutation; Abnormal chromosome C11; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19981029)78:3<306::AID-IJC8>3.0.CO;2-Z

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 β‐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. Int. J. Cancer 78:306–309, 1998.© 1998 Wiley‐Liss, Inc.