Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5.
Genomic imprinting at 11p15 is suggested to play a role in certain pediatric 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 lung, breast, and bladder cancers, possible involvement of genomic imprinting in these tumors has not been investigated extensively. p57KIP2, a newly described member of the p21 cyclin-dependent kinase (CDK) inhibitor family which is thought to negatively regulate the cell cycle at the G1 checkpoint, has been mapped to 11p15. In the present study, we searched for somatic p57KIP2 mutations in lung cancer, but failed to find such alterations. Interestingly, however, we found that the p57KIP2 gene is imprinted with maternal expression and that the maternal alleles had been selectively lost in 11 of 13 (85%) lung cancer cases carrying 11p15 deletions, this being a significant bias (p=0.01). These data provide the first evidence that genomic imprinting may play a role in the oncogenesis of not only rare pediatric tumors but also this common cancer of adults, suggesting that the imprinted p57KIP2 CDK inhibitor gene is a potential target for maternally biased 11p15 deletions.
Kondo
M
M
Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan.
Matsuoka
S
S
Uchida
K
K
Osada
H
H
Nagatake
M
M
Takagi
K
K
Harper
J W
JW
Takahashi
T
T
Elledge
S J
SJ
Takahashi
T
T
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57; D005260:Female; D017353:Gene Deletion; D018392:Genomic Imprinting; D006801:Humans; D008168:Lung / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014158:Transcription, Genetic
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins