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Frequent somatic mutations of GATA3 in non-BRCA1/BRCA2 familial breast tumors, but not in BRCA1-, BRCA2- or sporadic breast tumors

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Abstract

Heterozygous somatic mutations of the transcription factor, GATA-3, have recently been reported in approximately 5% breast of tumors unselected for family history. We sequenced the GATA-3 gene in 55 breast tumors from women with familial breast cancer, and found seven heterozygous somatic mutations, all in non-BRCA1/2 cases in which the frequency was 22%. In contrast, we found mutations of GATA-3 in only 4% of 81 sporadic tumors analysed. It is possible that GATA3 mutations occur earlier in the evolution of BRCAx tumors, compared to BRCA1, BRCA2 or sporadic tumors, and are therefore easier to detect by direct sequencing in the presence of some stromal contamination.

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Acknowledgments

We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704 and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. We would also like to thank Anna Marsh for technical assistance. GCT is a Senior Principal Research Fellow, and IGC is a Senior Research Fellow, of the NHMRC.

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Authors and Affiliations

  1. Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, QLD, Australia, 4029

    Jeremy M. Arnold, Nic Waddell & Georgia Chenevix-Trench

  2. Victorian Breast Cancer Research Consortium, Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

    David Y. H. Choong, Ella R. Thompson & Ian G. Campbell

  3. Victorian Breast Cancer Research Consortium, Walter and Eliza Hall Institute, Melbourne, VIC, Australia

    Geoffrey J. Lindeman & Jane E. Visvader

  4. Department of Pathology, University of Melbourne, Melbourne, VIC, Australia

    Ian G. Campbell

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  1. Jeremy M. Arnold
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  2. David Y. H. Choong
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  3. Ella R. Thompson
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  8. Georgia Chenevix-Trench
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Correspondence to Georgia Chenevix-Trench.

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Arnold, J.M., Choong, D.Y.H., Thompson, E.R. et al. Frequent somatic mutations of GATA3 in non-BRCA1/BRCA2 familial breast tumors, but not in BRCA1-, BRCA2- or sporadic breast tumors. Breast Cancer Res Treat 119, 491–496 (2010). https://doi.org/10.1007/s10549-008-0269-x

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