Assembly of whole-organ histologic and genetic maps
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March 2002
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A. An example of marker tested on multiple mucosal
samples from the cystectomy specimen (map 5). Marker IRF1 shows
loss of heterozygosity (LOH) in samples corresponding to TCC (samples
4, 15, and 16) as well as ones exhibiting changes consistent with
LGIN (samples 13, 19, 22, and 27) and HGIN (samples 2, 3, 5-12,
14, 17, 18, 20, 21, 23, 24, 26, 28-35). Sample No. 1 represents
allelic patterns of the same marker from peripheral blood of the
same patient and serves as control. The presence of LOH in all samples
was confirmed by densitometry and is expressed as O.D. ratio below
each sample in both panels. O.D.<0.5 is indicative of LOH.
B. Example of chromosome 5 allelic losses in a single
cystectomy specimen (map 5) with invasive non-papillary urothelial
carcinoma assembled by nearest neighbor analysis. The vertical axis
represents a chromosome 5 map showing positions of markers and their
chromosomal locations. Only altered markers are shown. The shaded
blocks represent areas of urinary bladder mucosa with LOH as they
relate to progression of neoplasia presented by a histologic map
of cystectomy in the background. Note: several markers, including
IRF1, show LOH in a form of a plaque involving a large area of urinary
bladder mucosa. Code for a histologic map is shown in B.
C. Examples of LOH distributions superimposed on
a histologic map of cystectomy specimen (map 5). Markers D5S346
and IRF1 show a plaque-like LOH involving almost all of the urinary
bladder mucosa. Marker D5S1465 shows LOH involving smaller area
of urinary bladder mucosa located within a larger plaque of LOH
which involved markers D5S346 and IRF1. Open boxes delineated by
lines indicate areas of urinary bladder mucosa with alterations
in a given locus. The background shadowed area represents a histologic
map of cystectomy specimen depicting distribution of various intraurothelial
precursor conditions and TCC. Histologic map code: (NU) normal urothelium;
(MD) mild dysplasia; (MdD) moderate dysplasia; (SD) severe dysplasia;
(CIS) carcinoma in situ; (TCC) invasive transitional cell carcinoma.
Reprinted with permission from Laboratory Investigation (2001;81[7]:1039).
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