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Loss of Heterozygosity in Sporadic Human Breast Carcinoma: A Common Region between 11q22 and 11q23.3¹

Molecular Genetics Laboratory, Salk Institute for Biological Studies, La Jolla, California 92318-5800 [G. M. H., G. A. E.]; Ludwig Institute for CancerResearch [R. W., I. N., W. K. C.], Department of Medicine [I. N., W. K. C.], and Center for Molecular Genetics [W. K. C.], University of California at San Diego, La Jolla, California 92093-0660; Departments of Medical Genetics [R. W., A. M.], Surgery [H. K.], Pathology [M. A.], and Oncology and Radiotherapy [R. W., G. B., P. J. T.], University of Oulu, FIN-90220 Oulu, Finland

The development of sporadic human breast cancer is associated with the accumulation of genetic alterations on several chromosomes. In the case of chromosome 11, loss of heterozygosity (LOH) at loci on the short arm has been well documented and suggests the presence of a suppressor gene(s) at 11p15.5. However, the evidence for similar events on the long arm is less compelling. Here, we determined the prevalence of LOH for chromosome 11q in 44 malignant and 3 benign cases of unselected sporadic breast tumor samples. We found that alteration of chromosome 11q is common in the pathogenesis of breast cancer as 19 of 44 (43%) malignant tumor specimens exhibited LOH. Eleven (58%) of these genetic alterations were specific to the long arm of the chromosome. The smallest region of shared LOH places the target between 11q22 and 11q23.3, the same general region frequently altered in cancers of the ovary, colon, skin, and uterine cervix, perhaps indicating the location of a tumor suppressor gene or genes of importance in each of these different tumor types.

¹ This study is supported in part by grants from the NIH (HG00202), the Department of Energy, the Harold G. and Leila Y. Mathers Foundation (G. A. E.), the Medical Research Council of the Academy of Finland (R. W.), the Ella and Georg Ehrnrooth Foundation (R. W.), and the University of Oulu (R. W., A. M., M. A., G. B., P. J. T., H. K.).

² Recipient of a long-term fellowship from the Human Frontier for Science Program.

³ To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research, San Diego Branch, 9500 Gilman Drive, La Jolla, CA 92093-0660.

Received 5/19/94. Accepted 7/15/94.

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