Mechanism of inactivation of @entity986 and XXXX in @entity1149 and association with advanced stage.

@entity1 @entity986 @entity5 @entity9288 @entity1149 @entity3
The @entity986 @entity5 suppressor gene encodes an inhibitor of type D cyclin dependent kinases. @entity986 is homozygously deleted in approximately 25% of @entity1149 ( @entity1149 ) cell lines and these deletions are associated with advanced stage @entity5 . Conflicting reports of the frequency of @entity986 alterations in @entity1149 prompted us to examine the relationship of these alterations and those of the related gene, @entity9288 , with @entity1 stage and site of @entity5 . One hundred twenty-five @entity1149 samples (71 cell lines and 54 @entity5 ) were examined by PCR-SSCP. Twenty of 71 (28%) @entity5 cell lines had homozygous deletions, and six (8%) had point mutations compared to 4 (7%) with point mutations among 54 @entity5 samples. All mutations were observed in @entity5 or cell lines from @entity1 with @entity5 . Two @entity1 with no mutations in their primary @entity5 had a @entity986 point mutation detected in a @entity3 . Point mutations were G:C to T:A transversion on the coding strand in five of 10 and resulted in nonsense mutations in seven of 10. Undetectable @entity986 mRNA, in the absence of detectable genetic alteration, was noted in a similar fraction of cell lines derived from @entity1 with stage I or II disease [two of seven (29%)] and @entity5 [15 of 49 (31%)]. Homozygous deletion of @entity9288 was found in 17 of 20 cell lines with @entity986 deletions; no point mutations of @entity9288 were identified by SSCP in the 125 samples. Thus, @entity986 is a frequent target of genetic alterations at 9p21 in @entity1149 . Both deletions and point mutations of @entity986 are closely associated with @entity5 dissemination.
