Absence of PTEN repeat tract mutation in endometrial cancers with microsatellite instability

Objective. PTEN, a tumor suppressor gene shown to be frequently mutated in endometrial cancers, has been suggested to be a target of microsatellite in stability (MSI)-driven mutagenesis. We set out to investigate the relations hip between MSI and PTEN mutation in a large series of primary endometrial carcinomas. Methods. Thirty-nine MSI-positive endometrial cancers were evaluated by sin gle-strand conformational variant analysis and direct sequencing to screen all nine PTEN exons for mutation. Results. Fifteen specimens (38%) demonstrated 16 PTEN mutations. We observe d only one alteration in the poly-adenine repeat of exon 8 that is suggeste d to be a target for mutation in endometrial cancers with MSI. Seven of 16 (44%) mutations in our series were deletions of greater than or equal to 3 bp, a class of mutation not usually associated with tumors with defective D NA mismatch repair. To determine the significance of this high frequency of deletion, 26 additional endometrial cancers without MSI were matched with the 39 MSI-positive cancers for the prognostic factors of tumor histology, stage, grade, and patient race. The MSI-positive tumors had a significantly higher frequency of deletions involving greater than or equal to 3 bp when compared with the MSE-negative group (5/11 versus 0/10, P = 0.035). Conclusions. Repeat tract mutation in PTEN is an uncommon event in MSI-posi tive cancers. Deletion of greater than or equal to 3 bp in this gene is mor e common in MSI-positive cancers when compared with tumors without MSI. (C) 2000 Academic Press.