Mutational analysis of the PTEN gene in human uterine sarcomas.
OBJECTIVE
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.


METHODS
Single-strand conformation analysis and direct sequencing of deoxyribonucleic acid were used to screen for PTEN mutations.


RESULTS
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.


CONCLUSIONS
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.
Lancaster
J M
JM
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Risinger
J I
JI
Carney
M E
ME
Barrett
J C
JC
Berchuck
A
A
D002461:Cell Line, Transformed; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D006801:Humans; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012509:Sarcoma / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014594:Uterine Neoplasms / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human