Genetic model of
human urothelial carcinogenesis
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Outer circle represents chromosomal vectors aligned clockwise from
p to q arms, with positions of altered markers exhibiting loss of heterozygosity
(LOH). All the markers are positioned on the vectors according to the human
genome database (version March 14, 1996). The innermost concentric circles represent
major phases of development and progression of urothelial neoplasia from normal
urothelium (NU) through low-grade intraurothelial neoplasia (LGIN) and high-grade
intraurothelial neoplasia (HGIN) to transitional cell carcinoma (TCC). Solid
circles denote statistically significant LOH of the markers defined by the logarithm
of odds score analysis. Open circles identify LOH without statistically significant
association to a given stage of neoplasia. The positions of open or solid circles
on appropriate concentric circles relate the alterations to a given phase of
neoplasia. Only markers with LOH are positioned on the chromosomal vectors.
Solid bars on outer brackets represent clusters of markers with significant
LOH and denote location of putative tumor suppressor genes involved in urothelial
neoplasia. The distances of markers on chromosomal vectors and the solid bars
depicting minimal deleted regions were adjusted to fit the circle and are not
drawn to scale. More precise localization of these regions can be obtained from
individual chromosomal vectors.
Reprinted by permission of Wiley-Liss Inc., a subsidiary of John Wiley
& Sons Inc. Czerniak B, et al. Genetic modeling of human urinary bladder carcinogenesis.
Genes Chromosomes Cancer. 2000;27:392-402.