Figure 4

Whole-organ histologic and genetic maps. (a) The histologic map of the entire bladder mucosa showing a distribution of intraurothelial neoplastic lesions and invasive cancer is illustrated. For the purpose of statistical analysis, intraurothelial precursor conditions were classified into two groups: low-grade intraurothelial neoplasia (mild to moderate dysplasia, LGIN) and high-grade intraurothelial neoplasia (severe dysplasia and carcinoma in situ, HGIN). The areas of bladder mucosa that were involved by clonal allelic losses of markers D3S1541 and D12S397 are delineated by interrupted and continuous red lines, respectively. The positions of these markers on the sex-averaged recombination-based map of chromosomes 3 and 12 as well as their band positions are shown on the left. (b) Examples of allelic patterns for the two markers (D12S397 and D3S1541) that were tested on mucosal samples (numbered 1–13) are illustrated. Sample no. 1 shows the allelic pattern of the same marker from peripheral blood lymphocytes (PBDNA) of the same patient. (c) Markers exhibiting clonal losses associated with early and late phases of in situ bladder neoplasia were identified using a computer algorithm that searched for overlapping plaques that matched the areas of bladder mucosa, with NU and LGIN contiguous to areas of HGIN and TCC (gray blocks). The allelic patterns of markers in mucosal samples were compared to their patterns in peripheral blood lymphocytes of the same patient. The chromosomal regions showing allelic losses restricted to later phases of neoplasia were identified by an algorithm that searched for overlapping plaques of losses restricted to HGIN that had progressed to TCC (red blocks). Markers with non-clonal losses involving smaller independent areas of the mucosa with no geographic relationship to in situ neoplasia or invasive cancer were eliminated from the diagram. (Modified and reprinted with permission from Lee S, Jeong J, Majewski T, et al. Proc Natl Acad Sci USA 2007;104:13732–13737.)