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 consis tent cytogenetic abnormalities found in human breast carcinoma. Overex pression of a large number of genes, because of acquisition of additio nal 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 muc in gene located at 1q21-q24. This gene is highly expressed in breast t umors, 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 dosag e and expression of the MUC1 gene. A correlation was found between acq uisition of additional copies of MUC1 gene and high mRNA levels (p < 0 .0001). These results identify a genetic mechanism responsible for MUC 1 gene overexpression and support the hypothesis that a gene dosage ef fect of the long arm of chromosome I may be involved in the pathogenes is of breast cancer. (C) Elsevier Science Inc., 1997.