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Refinement of Regional Loss of Heterozygosity for Chromosome 11p15.5 in Human Breast Tumors¹

Ludwig Institute for Cancer Research [R. W., I. N., W. C.], Department of Medicine [I. N., W. C.] and Center for Molecular Genetics [W. C.], University of California at San Diego, La Jolla, California 92093-0660; Departments of Medical Genetics [R. W., A. M.] and Surgery [H. K.], Oulu University Hospital, FIN-90220 Oulu, Finland; and Departments of Pathology [M. A.] and Oncology and Radiotherapy [R. W., G. B., P. J. T.], University of Oulu, FIN-90220 Oulu, Finland

² To whom requests for reprints should be addressed, at the Ludwig Institute for Cancer Research, San Diego Branch, 9500 Gilman Dr., La Jolla, CA 92093-0660.

The familial association of breast cancer with other tumors such as rhabdomyosarcoma that show loss of heterozygosity (LOH) for chromosome 11p15 as well as limited analyses showing LOH for chromosome lip in breast tumors suggests the presence of a pleiotropic tumor suppressor gene in this region. In order to test this idea, we analyzed DNA samples for 50 matched normal and tumor tissues from unselected breast cancer patients for LOH at loci throughout the chromosome 11p15.5 region. We found that 12.5% of informative cases showed LOH at HRAS1, 26.8% at TH, and 33.3% at both D11S860 and HBB, providing genetic support for this hypothesis. In contrast to previous observations which excluded the involvement of 11p15.5 regions distal to the HBB cluster, our results indicate that the subregion between TH and HBB is a critical region in breast cancer. This region is identical to that identified for the clinically associated tumor, rhabdomyosarcoma, and thus warrants intensive molecular analysis.

¹ Supported in part by grants from the Medical Research Council of the Academy of Finland, the University of Oulu, and the Ella & Georg Ehrnrooth Foundation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/26/93. Accepted 8/17/93.

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