[Frontiers in Bioscience 3, d944-960, September 1, 1998]
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CAVEAT LECTOR




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BIOLOGICAL AND MOLECULAR BASIS OF HUMAN BREAST CANCER

Jose Russo, Xiaoqi Yang, Yun-Fu Hu, Betsy A. Bove, Yajue Huang, Ismael D.C.G. Silva, Quivo Tahin, Yuli Wu, Nadia Higgy, Abdel Zekri, and Irma H. Russo

Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

Received 12/17/97 Accepted 7/21/98

8. GENOMIC CHANGES IN HUMAN BREAST LESIONS

In order to test whether similar changes of microsatellits are present in human breast carcinogenesis in vivo, we have also done microsatellite polymorphism analysis in genomic DNA extracted from breast lesions of three different categories: ductal hyperplasia (DHP), carcinoma in situ (CIS), and invasive carcinoma (INV). Using the array of 7 markers including D11S912, D11S940, D13S260, D13S289, D13S267, D16S285 and D17S855, we analyzed samples from 21 patients (Table 3) (119). Among these markers, D11S912 showed MSI in 10/19 (53%) of all samples including 2/8 of the preneoplastic lesion DHP, 8/15 of CIS, and 3/5 of INV (Figure 10; Table 3), in agreement with its early appearance in the transformed HBEC (i.e., BP1 cells) (see above). MSI of marker D13S260, which was absent in DHP, but present in 5/16 (31%) and 3/4 (75%) of CIS and INV, respectively (Figure 10; Table 3), suggesting a correlation with the progression and also a consistence with its alteration in the transformed HBEC (i.e., BP1E cells). In addition, the high MSI incidence in all samples for markers D11S912 (53%), D13S260 (23%), D13S289 (36%) and D13S267 (45%), as compared to lower rates of D11S940 (10%), D16S285 (6%) and D17S855 (9%) (Table 3) may suggest that instability may prefer to occur in these loci during breast carcinogenesis, also in good agreement with the data from the transformed HBEC system (except for D13S267).

Table 3. Microsatellite instability in human breast lesions

MARKER

Type

TOTAL

%

DHP*

%

CIS

%

INV

%

D11S912

di

10/19

53

2/8

25

8/15

53

3/5

33

D11S940

di

2/20

10

0/9

0

1/16

6

1/5

20

D13S289

di

4/11

36

0/5

0

2/7

29

2/2

100

D13S260

di

5/19

23

0/7

0

5/16

31

3/4

75

D13S267

di

9/20

45

1/7

14

9/16

56

2/4

50

D16S285

di

1/16

6

0/4

0

1/15

7

0/3

0

D17S855

di

1/11

9

0/4

0

0/8

0

1/4

25

Notes: *DHP: ductal hyperplasia; CIS: carcinoma in situ; INV: invasive carcinoma; di: dinucleotide repeats.