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Refined mapping of the region of loss of heterozygosity on the long arm of chromosome 7 in human breast cancer defines the location of a second tumor suppressor gene at 7q22 in the region of the CUTL1 gene

Abstract

In breast cancer, loss of heterozygosity (LOH) has been described on the long arm of chromosome 7, at band q31, suggesting the presence of a tumor suppressor gene in this region. In this study, we have identified a second region of LOH on 7q, at band 7q22. Deletion of genetic material at 7q22 was found in all tumor types and grades and was associated with increased tumor size. The region of LOH at 7q22 in every case included one or more of three polymorphic markers that are located within the CUTL1 gene. LOH of 7q22 has also been documented in the case of human uterine leiomyomas (Zeng et al., 1997; Ishwad et al., 1997). Interestingly, in both leiomyomas and mammary tumors induced in transgenic mice expressing the Polyomavirus (PyV) large T (LT) antigen, immunocomplexes of CUTL1 and PyV LT antigen were detected (Webster et al., 1998). Altogether, genetic data in human breast cancer and biochemical analyses in breast tumors from transgenic mice suggest that CUTL1 is a candidate tumor suppressor gene.

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Acknowledgements

We are grateful to Drs Irene Andrulis and Ivan Bièche for allowing us to use samples collected respectively at the Mount Sinai Hospital in Toronto, Canada and the Centre René Huguenin, Saint-Cloud, France. Thanks are also due to Jo-Ann Bader for advice on deparaffinization, and Lam Leduy for the mapping of polymorphic markers and processing the tumors used in this study. This research was funded by an operating grant to AN from the US Army Medical Research and Materiel Command (USAMRMC) as part of the Breast Cancer Research Program (BCRP). AN is the recipient of a scholarship from Le Fonds de la Recherche en Santé du Québec. WRZ is the recipient of studentships from the Alexander McFee Studentship, the McGill University Department of Medicine Internal Studentship, and the Research Institute of the Royal Victoria Hospital Studentship.

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Zeng, W., Watson, P., Lin, J. et al. Refined mapping of the region of loss of heterozygosity on the long arm of chromosome 7 in human breast cancer defines the location of a second tumor suppressor gene at 7q22 in the region of the CUTL1 gene. Oncogene 18, 2015–2021 (1999). https://doi.org/10.1038/sj.onc.1202519

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