Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas

PTEN is a novel tumour-suppressor gene located on chromosomal band 10q23.3. This region displays frequent loss of heterozygosity (LOH) in a variety of human neoplasms including breast carcinomas. The detection of PTEN mutatio ns in Cowden disease and in breast carcinoma cell lines suggests that PTEN may be invoked in mammary carcinogenesis. We here report a mutational analy sis of tumour specimens from 103 primary breast carcinomas and constitutive DNA from 25 breast cancer families. The entire coding region of PTEN was s creened by single-strand conformation polymorphism (SSCP) analysis and dire ct sequencing using intron-based primers. No germline mutations could be id entified in the breast cancer families and only one sporadic carcinoma carr ied a PTEN mutation at one allele. In addition, all sporadic tumours were a nalysed for homozygous deletions by differential polymerase chain reaction (PCR) and for allelic loss using the microsatellite markers D10S215, D10S56 4 and D10S573. No homozygous deletions were detected and only 10 out of 94 informative tumours showed allelic loss in the PTEN region. These results s uggest that PTEN does not play a major role in breast cancer formation.