We set out to determine the relative timing of loss of DNA mismatch repair and @entity984 mutation in endometrial tumorigenesis. We studied @entity1204 ( @entity189 ) and synchronous @entity1869 ( @entity1869 ), the premalignant precursor of @entity1204 . @entity189 and @entity1373 were investigated for loss of mismatch repair as evidenced by @entity124 ( @entity124 ) and for @entity984 mutations. @entity1204 previously shown to be @entity124 -positive were evaluated for @entity984 codon 12 and 13 mutations. DNA was isolated from foci of @entity1869 concomitant with, but physically remote from, the @entity5 by use of tissues prepared by laser capture microdissection (LCM). The @entity1869 DNAs were then assessed for @entity124 and @entity984 mutations. Of 210 endometrial CAs investigated, 51 (26%) were @entity124 -positive, and among those, 21 (41%) arose concomitantly with @entity1869 . Of 41 foci of @entity1869 (mean, two foci per @entity1 ) investigated, 34 (83%) were @entity124 -positive. @entity984 mutations were seen in 5/51 (10%) @entity189 . From the five @entity1 informative for both @entity984 mutation and @entity124 , 10 foci of @entity1869 were available for investigation. All 10 @entity1869 specimens (100%) were @entity124 -positive, and six (60%) had the @entity984 mutation present in the coexisting @entity189 . The observation that some @entity124 -positive @entity1869 specimens lack the @entity984 mutation seen in the coexisting @entity189 supports a model in which loss of DNA mismatch repair precedes @entity984 mutation. However, in addition to the absence of @entity984 mutations in @entity1869 , we discovered mutations in @entity1373 and @entity189 specimens that were not present in the portion of the @entity5 originally investigated. These discordant genotypes suggest genetic heterogeneity in @entity1204 .

Genotypic and phenotypic progression in endometrial tumorigenesis: determining when defects in DNA mismatch repair and XXXX occur.

@entity1204 :: ('MESH:D016889', 'Disease') :: ['endometrial carcinoma', 'endometrial hyperplasia and concomitant cancer', 'endometrial cancer', 'Endometrial cancers'] @entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity124 :: ('MESH:D053842', 'Disease') :: ['MSI', 'microsatellite instability'] @entity984 :: ('3845', 'Gene') :: ['KRAS2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['LCM hyperplasia', 'hyperplasia'] @entity189 :: ('MESH:D002277', 'Disease') :: ['Carcinoma', 'MSI-positive carcinomas', 'carcinoma', 'CA'] @entity1869 :: ('MESH:D004714', 'Disease') :: ['atypical endometrial hyperplasia', 'AEH']
@entity984 :: (3845,Gene) :: ['KRAS2']
