Mutational analysis of the PTEN gene in human uterine sarcomas.

Abstract

Uterine sarcomas are rare, lethal cancers, and little is known about their molecular etiology. The PTEN gene is located on chromosome 10q23.3, a region that displays frequent loss of heterozygosity in human uterine sarcomas. PTEN mutations have been described in 40% to 60% of uterine adenocarcinomas. To determine whether the PTEN gene is involved in the pathogenesis of uterine sarcoma, we analyzed deoxyribonucleic acid from uterine sarcomas and cell lines. Single-strand conformation analysis and direct sequencing of deoxyribonucleic acid were used to screen for PTEN mutations. Silent polymorphisms were detected in 2 of 36 primary uterine sarcomas. A 4-base pair deletion and a point mutation producing a stop codon were identified in 1 cell line. Mutational inactivation of PTEN does not play a major role in uterine sarcoma tumorigenesis, and another gene or genes on chromosome 10q may be implicated as a cause of these cancers. Differences in the molecular alterations underlying the development of uterine sarcomas and adenocarcinomas are significant.