SELECTIVE MATERNAL-ALLELE LOSS IN HUMAN LUNG CANCERS OF THE MATERNALLY EXPRESSED P57(KIP2) GENE AT 11P15.5

Genomic imprinting at 11p15 is suggested to play a role in certain ped iatric tumors such as Wilms' tumor, based on the findings of selective maternal loss of this chromosomal region, Although the allele loss at 11p15 is also frequent in a number of cancers of adults including lun g, breast, and bladder cancers, possible involvement of genomic imprin ting in these tumors has not been investigated extensively, p57(KIP2), a newly described member of the p21 cyclin-dependent kinase (CDK) inh ibitor family which is thought to negatively regulate the cell cylce a t the G(1) checkpoint, has been mapped to 11p15, In the present study, we searched for somatic p57(KIP2) mutations in lung cancer, but faile d to find such alterations, Interestingly, however, we found that the p57(KIP2) gene is imprinted with maternal expression and that the mate rnal alleles had been selectively lost in 11 of 13 (85%) lung cancer c ases carrying 11p15 deletions, this being a significant bias (P=0.01), These data provide the first evidence that genomic imprinting may pla y a role in the oncogenesis of not only rare pediatric tumors but also this common cancer of adults, suggesting that the imprinted p57(KIP2) CDK inhibitor gene is a potential target for maternally biased 11p15 deletions.