Cyclin-dependent kinase inhibitor p57KIP2 in soft tissue sarcomas and Wilms'tumors.
Mammalian cyclin-dependent kinase inhibitors fall into two families, the INK4 and the CIP/KIP. The CIP/KIP family comprises three structurally related members, including p21CiP1/WAF1, p27KIP1, and p57KIP2. These proteins are all capable of inhibiting the progression of the cell cycle by binding and inhibiting G(1) cyclin/cyclin-dependent kinase complexes. In humans, p57KIP2 is expressed specifically in skeletal muscle, heart, brain, kidney, and lung. Human KIP2 resides in 11p15.5, a chromosomal region that is a common site for loss of heterozygosity in certain sarcomas, Wilms' tumors, and tumors associated with the Beckwith-Wiedemann syndrome. Because of the function, selective expression, and chromosomal location of p57KIP2, we undertook the present study to search for potential mutations of KIP2 in a cohort of 126 tumors composed of 75 soft tissue sarcomas and 51 Wilms' tumors. The KIP2 gene was characterized by Southern blot, comparative multiplex PCR, PCR -single-strand conformational polymorphism, and DNA sequencing assays in these neoplasms. Deletions of the KIP2 gene or point mutations at the region encoding the cyclin-dependent kinase inhibitory domain were not found in the tumors analyzed. The absence of KIP2 mutations might indicate that these tumors arise due to defects at a closely linked but separate locus. Alternatively, similarly to the mouse homologue, inactivation of KIP2 could occur via genomic imprinting.
Orlow
I
I
Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Iavarone
A
A
Crider-Miller
S J
SJ
Bonilla
F
F
Latres
E
E
Lee
M H
MH
Gerald
W L
WL
Massagué
J
J
Weissman
B E
BE
Cordón-Cardó
C
C
D000328:Adult; D001483:Base Sequence; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016162:Genes, Wilms Tumor / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012509:Sarcoma / Q000737:chemistry* / Q000235:genetics; D009396:Wilms Tumor / Q000737:chemistry* / Q000235:genetics
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009363:Neoplasm Proteins; D009687:Nuclear Proteins