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Prevalence of Estrogen Receptor Variant Messenger RNAs in Human Breast Cancer¹

Departments of Biochemistry and Molecular Biology [E. L., L. C. M.] and Pathology [A. H., P. H. W.], University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba MB R3E OW3, Canada

A new approach, based on the competitive amplification of wild-type and exon-deleted estrogen receptor (ER) variant cDNAs, was used to screen 100 human breast tumors for the presence of ER variants. Already described exon 4-deleted ER mRNA was preferentially detected in tumors with lower grades (P < 0.05) or higher progesterone receptor levels (P < 0.01), whereas new ER variants, deleted in exons 2–4 or in regions within exons 3–7 were associated with higher grades (P < 0.025) and higher ERs (P < 0.001). This approach allows investigation of the expression of multiple ER variant mRNAs and may implicate them as new prognostic markers and as possible contributors to tumor progression.

¹ This work was supported by grants from the Canadian Breast Cancer Research Initiative and the U.S. Army Medical Research and Material Command. The Manitoba Breast Tumor Bank is supported by funding from the National Cancer Institute of Canada and the Terry Fox Foundation. P. H. W. is a Medical Research Council of Canada Clinician-Scientist; L. C. M. is an MRC Scientist; and E. L. is a recipient of the U.S. Army Medical Research and Material Command Postdoctoral Fellowship.

² To whom requests for reprints should be addressed. Phone: (204) 789-3812; Fax: (204) 783- 0864.

Received 7/11/96. Accepted 8/15/96.

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