title: Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma.
abstract: In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University Medical Center, University Hospital 3465, 550 North University Boulevard, Indianapolis, Indiana 46202, USA. lcheng@iupui.edu
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Jones
authors.forename: Ryan P
authors.initials: RP
authors.lastname: McCarthy
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Ximing J
authors.initials: XJ
authors.lastname: Yang
authors.forename: Michael O
authors.initials: MO
authors.lastname: Koch
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baldridge
mesh_terms: D000368:Aged; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D041321:Chromosomes, Human, X; D002999:Clone Cells; D005260:Female; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D008967:Molecular Biology; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*