Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15.
Parental origin-specific alterations of chromosome 11p15 in human cancer suggest the involvement of one or more maternally expressed imprinted genes involved in embryonal tumor suppression and the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). The gene encoding cyclin-dependent kinase inhibitor p57KIP2, whose overexpression causes G1 phase arrest, was recently cloned and mapped to this band. We find that the p57KIP2 gene is imprinted, with preferential expression of the maternal allele. However, the imprint is not absolute, as the paternal allele is also expressed at low levels in most tissues, and at levels comparable to the maternal allele in fetal brain and some embryonal tumors. The biochemical function, chromosomal location, and imprinting of the p57KIP2 gene match the properties predicted for a tumor suppressor gene at 11p15.5. However, as the p57KIP2 gene is 500 kb centromeric to the gene encoding insulin-like growth factor 2, it is likely to be part of a large domain containing other imprinted genes. Thus, loss of heterozygosity or loss of imprinting might simultaneously affect several genes at this locus that together contribute to tumor and/or growth- suppressing functions that are disrupted in BWS and embryonal tumors.
Matsuoka
S
S
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Thompson
J S
JS
Edwards
M C
MC
Bartletta
J M
JM
Grundy
P
P
Kalikin
L M
LM
Harper
J W
JW
Elledge
S J
SJ
Feinberg
A P
AP
D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; D004791:Enzyme Inhibitors; D005260:Female; D016193:G1 Phase; D015870:Gene Expression; D018392:Genomic Imprinting; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D009396:Wilms Tumor / Q000378:metabolism
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins