A gene dosage effect is responsible for high overexpression of the MUC1 gene observed in human breast tumors

Alterations of the entire long arm of chromosome 1 are the most consistent cytogenetic abnormalities found in human breast carcinoma. Overexpression of a large number of genes, because of acquisition of additional copies of one arm or a whole chromosome, is one possible cause of the imbalance in cell metabolism. To investigate the existence of such a gene dosage effect in breast cancer, we chose to study the MUC1 mucin gene located at 1q21-q24. This gene is highly expressed in breast tumors, but the genetic mechanism for its ectopic overexpression is not clearly known. Thirty-two human primary breast tumors were examined, by Southern blot DNA and northern blot RNA analyses, for allelic dosage and expression of the MUC1 gene. A correlation was foundbetween acquisition of additional copies of MUC1 gene and high mRNA levels (p < 0.0001). These results identify a genetic mechanism responsible for MUC1 gene overexpression and support the hypothesis that a gene dosage effect of the long arm of chromosome 1 may be involved in the pathogenesis of breast cancer.