A HETEROZYGOUS GERMLINE MUTATION OF THE PTEN MMAC1 GENE IN A PATIENT WITH COWDEN-DISEASE/

Cowden disease, or multiple hamartoma syndrome, is an autosomal domina nt inherited cancer syndrome with a high risk of thyroid and breast ca ncers. Its susceptibility gene has been mapped to chromosome 10q22-23. Because a newly found tumor suppressor gene, PTEN/MMAC1, often mutate d in glioblastoma and in prostatic and breast cancers, has been mapped to the same chromosomal locus, it is suspected that it may be the gen e responsible for Cowden disease. Germline mutations of the gene have been reported in 4 of 5 families with Cowden disease. We performed a g enetic analysis of the PTEN/MMAC1 gene in a sporadically found patient with the disease who had no apparent family history of the disease. W e found a germline heterozygous mutation of the PTEN/MMAC1 gene in a p atient with Cowden disease. The mutation, a C to T substitution of a s ingle base at codon 130, leads to a formation of stop codon, generatin g a truncated protein lacking both protein phosphatase signature motif and tensin-like domain. Our finding supports the hypothesis of the PT EN/MMAC1 gene as being responsible for Cowden disease even in a sporad ic case.