Loss of imprinting and genetic alterations of the cyclin-dependent kinase inhibitor p57KIP2 gene in head and neck squamous cell carcinoma.
The p57KIP2 is a maternally expressed and paternally imprinted cyclin-dependent kinase inhibitor located on chromosome 11p15.5. Because of its location, biochemical functions, and imprinting status, p57KIP2 has been considered a candidate tumor suppressor gene. To determine, for the first time, the involvement of this gene in the development of head and neck squamous carcinoma (HNSC), we analyzed the imprinting and expression status and loss of heterozygosity (LOH) within the p57KIP2 gene flanking loci on the 11p15.5 region in 64 primary untreated tumors. Of the 30 (47%) informative cases for this gene, loss of imprinting and LOH were noted in 4 (13%) and 10 tumors (33%), respectively. Analysis of the microsatellite markers flanking the p57KIP2 gene on chromosome 11p showed infrequent alterations at these loci. p57KIP2 was expressed in all tumors with LOH within and around the gene. Quantitative reverse transcription-PCR analysis showed elevated p57 mRNA expression in tumor with loss of imprinting. Sequencing analysis of exons 1 and 2 of the p57KIP gene failed to detect any mutations. Our data indicate: (a) infrequent genomic abnormalities at the p57KIP2 gene in HNSC; (b) leaky or incomplete imprinting of the paternal allele is associated with increased expression of this gene in a subset of tumors; and (c) minimal evidence for suppressor function for this gene in HNSC.
Lai
S
S
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston 77583, USA.
Goepfert
H
H
Gillenwater
A M
AM
Luna
M A
MA
El-Naggar
A K
AK
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57; D005091:Exons; D015870:Gene Expression; D018392:Genomic Imprinting; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D012333:RNA, Messenger