INFREQUENT MUTATIONS IN THE PTEN MMAC1 GENE AMONG PRIMARY BREAST CANCERS/

Recently PTEN/MMAC1, a candidate tumor suppressor gene, was isolated f rom chromosome 10q23-24 and somatic mutations of this gene were detect ed in several malignancies including brain, prostate, and breast tumor s, To investigate further the potential role of this gene in mammary c arcinogenesis, we examined 69 primary breast cancers for mutations in PTEN/MMAC1 by means of polymerase chain reaction single-strand conform ation polymorphism and sequencing analysis, We detected only one somat ic missense mutation, a change from T to C at codon 59 (TCA to CCA) re sulting in substitution of Pro for Ser in the predicted protein, This site is located outside of phosphatase or phosphate-acceptor motifs, b ut this codon encodes a residue that is conserved in homologous protei ns, tensin and auxilin and is likely to be crucial for normal function of PTEN/MMAC1. Among the 69 tumors examined, three low-frequency poly morphisms were found as well, one in the non-coding region of exon 1 a nd one each in introns 2 and 7, Our results suggested that mutation of the PTEN/MMAC1 gene is not a major factor in the development of most primary breast cancers.