title: Karyotypic characterization of urinary bladder transitional cell carcinomas.
abstract: Samples from 34 primary transitional cell carcinomas (TCCs) of the bladder were short-term-cultured and processed for cytogenetic analysis after G-banding of the chromosomes. Clonal chromosome abnormalities were detected in 27 tumors and normal karyotypes in 3, and the cultures from 4 tumors failed to grow. Losses of genetic material were more common than gains, indicating that loss of tumor suppressor genes may be of major importance in TCC pathogenesis. There was no clonal heterogeneity within individual tumors, consonant with the view that TCCs are monoclonal in origin. The most striking finding was the involvement of chromosome 9 in 92% of the informative cases, as numerical loss of one chromosome copy in 15 cases, but as structural rearrangement in 8. The changes in chromosome 9 always led to loss of material; from 9p, from 9q, or of the entire chromosome. A total of 16 recurrent, unbalanced structural rearrangements were seen, of which del(1)(p11), add(3)(q21), add(5)(q11), del(6)(q13), add(7)(q11), add(11)(p11), i(13)(q10), del(14)(q24), and i(17)(q10) are described here for the first time. The karyotypic imbalances were dominated by losses of the entire or parts of chromosome arms 1p, 9p, 9q, 11p, 13p, and 17p, loss of an entire copy of chromosomes 9, 14, 16, 18, and the Y chromosome, and gains of chromosome arms 1q and 13q and of chromosomes 7 and 20. The chromosome bands and centomeric breakpoints preferentially involved in structural rearrangements were 1q12, 2q11, 5q11, 8q24, 9p13, 9q13, 9q22, 11p11, and 13p10. Rearrangements of 17p and the formation of an i(5)(p10) were associated with more aggressive tumor phenotypes. There was also a general correlation between the tumors' grade/stage and karyotypic complexity, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis.
authors.affiliation: Department of Clinical Genetics, University Hospital, Lund, Sweden. imad.elmula@klingen.lu.se
authors.forename: I
authors.initials: I
authors.lastname: Fadl-Elmula
authors.forename: L
authors.initials: L
authors.lastname: Gorunova
authors.forename: N
authors.initials: N
authors.lastname: Mandahl
authors.forename: P
authors.initials: P
authors.lastname: Elfving
authors.forename: R
authors.initials: R
authors.lastname: Lundgren
authors.forename: F
authors.initials: F
authors.lastname: Mitelman
authors.forename: S
authors.initials: S
authors.lastname: Heim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*