COMPARATIVE GENOMIC HYBRIDIZATION STUDY OF INVASIVE TRANSITIONAL CELL CARCINOMAS OF THE URINARY BLADDER OF BULGARIAN PATIENTS
Zaharieva B1, Damianov Ch2, Tabakov V2, Tzingilev B2, Nikolov I1, Georgiev Ch3, Toncheva D1
*Corresponding Author: Toncheva D. Department of Medical Genetics, Medical University Sofia, 2 Zdrave str, 1431 Sofia, Bulgaria Tel/Fax: + 359 2 9520357 email: draga@spnet.net
page: 31

RESULTS

CGH and tumor stage

The total number of aberrations in all tumors studied (pT1-4) ranged from 0 to 20 per case (mean, 4.19). Gains (range, 0-13; mean, 3.58) were more frequent than deletions (range, 0-7; mean, 0.62)(Table 1). Eight tumors had no detectable aberrations. Two tumors had single aberrations (7q+ and 9q+ respectively).

Stage pT1. pT1 tumors had an average number of 3.25 aberrations per case, ranging from 0 to 9). There were 0.13 deletions (range, 0-2) and 3.13 gains (range, 0-9). Seven out of 16 tumors (43.75%) had no detectable aberrations. No tumor showed a single aberration. No deletion was repeatedly found. Gain at 3q was the most frequent aberration (25%)(Table 2). Gains at 1q and 8q were found in 3 tumors (18.75%), while repeatedly in two tumors were gains at 2p, 2q, 3p, 6p, 6q, 8p, 10q, 12p, 12q, 16q, and 17q (12.5%). All aberrations of pT1 tumors are summarized in Fig. 1.

Stage pT2-4. pT2-4 tumors had higher number of aberrations than pT1 tumors (mean, 5.7; range 0-20). On average there were 1.4 deletions (range, 0-7) and 4.3 gains (range, 0-13). One tumor had no detectable aberrations (10%). Two tumors showed only one aberration (7q+ and 9q+ respectively). Repeatedly found aberrations were 17q+ (50%), 20q+ (40%), 5p+ (30%), 7q+ (30%), 15q+ (30%), 16q+ (30%), 9p- (20%), 3q+ (20%), 7p+ (20%), 12q+ (20%), and 20p+ (20%). All aberrations of pT2-4 tumors are summarized in Tables 1, 2 and Fig. 2.

Neither the total number of aberrations nor separately the number of deletions and gains reached statistically significant differences between pT1 and pT2-4 tumors (P=0.2030, P=0.0610, P=0.4350), although there was a trend towards increased genomic instability in muscle-invasive compared to minimally invasive bladder cancers. Most clear was the trend concerning the frequencies of deletions.

There was no significant difference between losses of none of the chromosomal regions. Gains at 5p and 20p were not found in pT1 tumors whereas they were repeatedly found in pT2-4 tumors (P=0.0198 and P=0.0626). The frequency of gains at 17q and 20q significantly increased in pT2-4 tumors compared to pT1 (P=0.0360 and P=0.0336). Summary of the results on affected chromosomal regions and tumor stage are shown in Table 2.

Table 1. Number of aberrations and tumor stage

Tumor stage

No.

Deletions a

Gains a

Total number of aberrations a

pT1

16

0.13 ± 0.50

3.13 ± 3.59

3.25 ± 3.59

pT2-4

10

1.40 ± 2.55b

4.30 ± 3.80c

5.70 ± 6.00d

Total

26

0.62 ± 1.70

3.58 ± 3.65

4.19 ± 4.71

a Aberrations per tumor (mean±SD)
b P=0.0610
c P=0.4350
d P=0.2030

CGH and tumor grade

The number of aberrations increased from grade 2 to grade 3 tumors (mean, 4.22; range, 0-20 for G2; and mean, 4.71; range, 0-10 for G3)(Table 3). The trend concerned both deletion and gains’ rate. However, the differences between G2 and G3 tumors were not significant neither in the number of deletions (P=0.8970) and gains (P=0.8410), nor in the total number of chromosomal aberrations (P=0.8210).

 


Table 2. Specific genomic alterations and tumor stage

Type of aberration

Locus

pT1 (Total n=16)
n (%)

pT2-4 (Total n=10)
n (%)

pa

Deletion

3q

0 (0%)

1 (10%)

0.1971

 

4q

0 (0%)

1 (10%)

0.1972

 

5p

0 (0%)

1 (10%)

0.1973

 

6p

0 (0%)

1 (10%)

0.1974

 

6q

0 (0%)

1 (10%)

0.1975

 

9p

1 (6.25%)

2 (20%)

0.2856

 

9q

1 (6.25%)

1 (10%)

0.7269

 

10q

0 (0%)

1 (10%)

0.1971

 

11p

0 (0%)

1 (10%)

0.1971

 

12p

0 (0%)

1 (10%)

0.1971

 

16q

0 (0%)

1 (10%)

0.1971

Gain

1q

3 (18.75%)

0 (0%)

0.1454

 

2p

2 (12.5%)

0 (0%)

0.2446

 

2q

2 (12.5%)

0 (0%)

0.2446

 

3p

2 (12.5%)

0 (0%)

0.2446

 

3q

4 (25.0%)

2 (20%)

0.7680

 

4q

1 (6.25%)

0 (0%)

0.4201

 

5p

0 (0%)

3 (30%)

0.0198b

 

5q

1 (6.25%)

0 (0%)

0.4201

 

6p

2 (12.5%)

1 (10%)

0.8454

 

6q

2 (12.5%)

0 (0%)

0.2446

 

7p

1 (6.25%)

2 (20%)

0.2856

 

7q

1 (6.25%)

3 (30%)

0.1025

 

8p

2 (12.5%)

0 (0%)

0.2446

 

8q

3 (18.75%)

1 (10%)

0.5474

 

9p

1 (6.25%)

0 (0%)

0.4201

 

9q

1 (6.25%)

1 (10%)

0.7269

 

10q

2 (12.5%)

0 (0%)

0.2446

 

11p

1 (6.25%)

0 (0%)

0.4201

 

11q

2 (12.5%)

1 (10%)

0.8454

 

12p

2 (12.5%)

1 (10%)

0.8454

 

12q

2 (12.5%)

2 (20%)

0.6060

 

13q

0 (0%)

1 (10%)

0.1971

 

14q

0 (0%)

1 (10%)

0.1971

 

15q

1 (6.25%)

3 (30%)

0.1025

 

16q

2 (12.5%)

3 (30%)

0.2707

 

17p

1 (6.25%)

0 (0%)

0.4201

 

17q

2 (12.5%)

5 (50%)

0.0360

 

18p

0 (0%)

1 (10%)

0.1971

 

18q

0 (0%)

1 (10%)

0.1971

 

20p

0 (0%)

2 (20%)

0.0626

 

20q

1 (6.25%)

4 (40%)

0.0336

 

21q

1 (6.25%)

1 (10%)

0.7269

a λ2 test




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