Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of XXXX .

@entity7465 @entity5 @entity1821 @entity8985
@entity1821 represents a unique model insofar as some well-differentiated @entity1821 progress to non-lipogenic, so-called 'dedifferentiated,' forms. The well-differentiated and dedifferentiated family of @entity1821 demonstrates amplification of the chromosome subregion 12q13-q15 with resultant amplification of the @entity7465 and @entity8985 genes. However, the specific genetic changes that distinguish between well-differentiated and @entity1821 are less well understood. To study the genetic changes in @entity1821 , @entity5 were analyzed separately by array-based comparative genomic hybridization. A bacterial artificial chromosome array at approximately 1-Mb resolution was used. The genetic changes were compared with clinical presentation, grade of the dedifferentiated component and overexpression of @entity7465 and @entity8985 . Most @entity5 (n=21, 72%) were retroperitoneal, with both components present at initial diagnosis (n=25, 86%). @entity5 (28%) were classified as low-grade dedifferentiation. In four cases (14%), a well-differentiated @entity1821 preceded the presentation of the dedifferentiated @entity5 by 1-5 years. 12q13-q15 was amplified in all @entity5 . Using unsupervised hierarchical clustering of copy-number changes, all but two @entity5 showed close similarities between well-differentiated and dedifferentiated components, and segregated as pairs. Dedifferentiated components had more total amplifications (P=0.008) and a trend for gain at 19q13.2, but no genetic changes were significant in distinguishing between the two components. High-level amplifications of 1p21-32 (n=7, 24%), 1q21-23 (n=9, 31%), 6q23-24 (n=6, 21%) and 12q24 (n=3, 10%) were common, but none significantly correlated with differentiation. Presentation and grade correlated with the frequency of changes at a number of genetic loci (P<0.001), whereas @entity8985 immunostaining showed negative correlation with 12q13.13 amplification. The genotypic similarity, at the limit of the array's resolution, between components implies that most genetic changes precede phenotypic 'progression,' early in tumorigenesis. The relationship between genetic changes and presentation or grade may reflect differences in factors that control genomic instability or the background genotype of the @entity5 .
