Frequency of the ATM IVS10-6T -> G variant in Australian multiple-case breast cancer families
- Author(s)
- Lindeman, GJ; Hiew, M; Visvader, JE; Leary, J; Field, M; Gaff, CL; Gardner, RJM; Trainor, K; Cheetham, G; Suthers, G; Kirk, J;
- Details
- Publication Year 2004,Volume 6,Issue #4,Page R401-R407
- Journal Title
- BREAST CANCER RESEARCH
- Publication Type
- Journal Article
- Abstract
- Background Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia-telangiectasia mutated (ATM) gene, IVS10-6T-->G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial. Methods We determined the frequency of ATM IVS10-6T-->G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics. Results Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T-->G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance. Conclusion These findings indicate that the ATM IVS10-6T-->G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes ( such as BRCA1) remains possible. Routine testing for ATM IVS10-6T-->G is not warranted in mutation screening of affected individuals from high-risk families.
- Publisher
- BIOMED CENTRAL LTD
- Keywords
- ATAXIA-TELANGIECTASIA HETEROZYGOTES; DOUBLE-STRAND BREAKS; DEPENDENT PHOSPHORYLATION; SUSCEPTIBILITY GENES; EARLY-ONSET; MUTATIONS; BRCA1; RISK; IVS10-6T-GREATER-THAN-G; CONTRIBUTE
- Publisher's Version
- https://doi.org/10.1186/bcr806
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Creation Date: 2004-01-01 12:00:00