IN PRIMARY HUMAN BREAST CARCINOMAS MUTATIONS IN EXONS-5 AND 6 OF THE P53 GENE ARE ASSOCIATED WITH A HIGH S-PHASE INDEX

A series of 121 human breast tumors was screened for point mutations i n exons 5 through 8 of the p53 gene, by SSCP analysis. On the same tum or samples, the S-phase index (SPI) was determined by the incorporatio n of BUdR in fresh tissue. p53 mutations were observed in 29% of the c ases. The frequency of point mutations for the individual exons was: e xon 5, 10.0%; exon 6, 9.9%; exon 7, 7. 1% and exon 8, 5.5%. Two mutati ons detected by SSCP were confirmed by sequencing the p53 cDNA. The pr esence of a p53 mutation, irrespective of its location, correlates (p = 0.003) with a high SPI. This association appears to primarily reflec t mutations in exon 5 (p = 0.0002) and exon 6 (p = 0.05), since mutati ons in exons 7 and 8 failed to show any association. These results ind icate that mutations in the pS3 gene identify highly proliferating tum ors, and that the position of the p53 mutation may have different effe cts upon the proliferative activity of tumor cells in vivo. (C) 1993 W iley-Liss, Inc.