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.