PARTIAL ALLELOTYPE OF CARCINOMA IN-SITU OF THE HUMAN BLADDER

Carcinoma in situ (CIS) of the urinary bladder is an aggressive lesion that frequently progresses to an invasive tumor, yet the underlying m olecular changes in this lesion are largely unknown. In this study, we microdissected 31 cases of CIS and examined them for loss of heterozy gosity (LOH) on 13 chromosomal arms, Twenty-nine microsatellite marker s mere chosen for this analysis based on their location in regions pre viously shown to be frequently lost in primary transitional cell carci noma of the bladder, LOH of chromosome 9 was a frequent event in these samples, occurring in 77% of these lesions, with 19 of 31 cases showi ng deletion on the 9p arm (61%) and 17 of 28 cases displaying LOH on 9 q (61%), Fine mapping at 9p21 demonstrated that CIS also displayed a h igh frequency of homozygous deletion surrounding the p16(INK4A) locus, like superficial papillary tumors, the other form of noninvasive lesi on found in the bladder, However, loss of 14q (70%) was frequent in CI S yet extremely rare in papillary lesions (9%), Other chromosomal arms showing frequent LOH included 8p (65%), 17p (60%), 13q (56%), 11p (54 %), and 4q (52%), whereas slightly lower frequencies of loss were obse rved for 11q (36%), 4p (32%), 3p (31%), 18q (29%), and 5q (20%), CIS l esions already possess many of the genetic alterations displayed by in vasive transitional cell carcinomas, potentially accounting for the ag gressive nature of these lesions.