Tumor-Suppressor Genes 
cancer-suppressing property of tumor-suppressor 
genes to identify the key chromosomal region 
containing the gene. In a test of this method, 8 of 
nearly 100 chromosome 11 superfragments that 
the laboratory isolated, when introduced into WT 
cells, suppressed their neoplastic growth. Inter- 
estingly, the tumor-suppressing hybrids contain a 
small portion of 1 lpl5, demonstrating the exis- 
tence of a suppressor gene on this band. The labo- 
ratory is now testing whether these superfrag- 
ments also suppress important common cancers 
that involve lip, such as lung cancer. This novel 
technique may allow investigators to bridge a gap 
in cloning methods between chromosome-size 
pieces (averaging 100 million nucleotides) and 
YACs (averaging 300,000 nucleotides), and it 
may have general application to cloning a wide 
variety of genes. 
Another long-standing interest of the labora- 
tory is the role of epigenetic changes (not involv- 
ing DNA sequence, and thus potentially re- 
versible) in cancer. The laboratory recently 
identified several CpG islands (DNA sequences 
rich in cytosine-guanine dinucleotides, often 
found near actively expressed genes) within the 
1 Ipl 3 WT gene region. Some of these sequences 
were methylated, a reversible modification of the 
nucleotide cytosine. Previously CpG islands 
were only known to be methylated on the inac- 
tive X chromosome. The surprising finding of 
methylated autosomal CpG islands suggests that 
epigenetic changes may play a role in Wilms' tu- 
morigenesis. We are now testing this hypothesis 
by examining the islands directly. 
We also observed that balanced BWS chromo- 
somal translocations on llpl5 always involve 
the maternal chromosome, while unbalanced 
BWS duplications always involve the paternal 
chromosome, suggesting an epigenetic differ- 
ence (or imprint) between the two alleles. If 
such epigenetic changes are found to contribute 
to inactivation of 1 Ip suppressor genes, this will 
represent an exciting convergence of our two 
major interests. 
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