p73, a protein that has substantial structural and functional similari
ty to p53, has recently been identified. It was found to be monoalleli
cally expressed in all cell lines and normal individuals tested, To el
ucidate its role in cancer development and as a potential imprinted tu
mor suppressor, we investigated the allele-specific expression of the
human p73 gene in 28 cases of renal cell carcinoma and its imprinting
status in fetal pancreatic and thymic tissues. Of 12 informative pairs
of renal cell carcinoma and matched normal tissues identified by StyI
restriction fragment length polymorphism (RFLP) in exon 2, p73 showed
monoallelic expression in 11 out of 12 normal tissues but biallelic e
xpression in 8/12 and switched allele expression in 2/12 of the matche
d corresponding cancers. An imprinting study of the p73 gene in two fa
milies using a newly identified exonic BanI RFLP indicated that expres
sion of p73 was limited to the maternal allele in RNA from fetal pancr
eas and thymus, demonstrating that p73 is imprinted in at least these
two tissues. These findings strongly suggest that loss of imprinting o
r switching of allelic expression of the p73 gene is associated with t
he development of renal cell carcinoma.