ISOLATION OF KIDNEY COMPLEMENTARY DNAS DOWN-EXPRESSED IN WILMS-TUMOR BY A SUBTRACTIVE HYBRIDIZATION APPROACH

We applied a subtractive hybridization approach to isolate genes diffe rentially expressed between mature kidney and Wilms' tumor. We constru cted a complementary DNA library from a total mature kidney complement ary DNA subtracted by an excess of mRNA from a Wilms' tumor, WAGR4, wi th a germline deletion of 11p13 and a somatic loss of alleles at 11p15 . Six clones presenting a differential pattern of expression, positive with mRNA from the mature kidney and negative with mRNA from the Wilm s' tumor WAGR4, were characterized. Among these clones were two as yet unknown expressed sequences (D11S877E and D15S109E) and four sequence s from known genes: renal dipeptidase (DPEP1), alphaB-crystallin (CRYA 2), uromodulin (UMOD), and plasma glutathione peroxidase (GPX2). The d ifferent patterns of expression of these genes in 11 Wilms' tumors, wh ether or not they are hereditary reflect the well-documented pathogene tic heterogeneity for Wilms' tumors. We propose that these clones coul d be helpful for an improved histological characterization of Wilms' t umors.