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

PTEN, a tumor suppressor gene shown to be frequently mutated in endometrial cancers, has been suggested to be a target of microsatellite instability (MSI)-driven mutagenesis. We set out to investigate the relationship between MSI and PTEN mutation in a large series of primary endometrial carcinomas.

Thirty-nine MSI-positive endometrial cancers were evaluated by single-strand conformational variant analysis and direct sequencing to screen all nine PTEN exons for mutation.

Fifteen specimens (38%) demonstrated 16 PTEN mutations. We observed only one alteration in the poly-adenine repeat of exon 8 that is suggested to be a target for mutation in endometrial cancers with MSI. Seven of 16 (44%) mutations in our series were deletions of >/=3 bp, a class of mutation not usually associated with tumors with defective DNA 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 >/=3 bp when compared with the MSI-negative group (5/11 versus 0/10, P = 0.035).

Repeat tract mutation in PTEN is an uncommon event in MSI-positive cancers. Deletion of >/=3 bp in this gene is more common in MSI-positive cancers when compared with tumors without MSI.