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Loss of Imprinting and Genetic Alterations of the Cyclin-dependent Kinase Inhibitor p57^KIP2 Gene in Head and Neck Squamous Cell Carcinoma¹

Departments of Pathology [S. L., M. A. L., A. K. E.] and Head and Neck Surgery [H. G., A. M. G.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77583

The p57^KIP2 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, p57^KIP2 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 p57^KIP2 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 p57^KIP2 gene on chromosome 11p showed infrequent alterations at these loci. p57^KIP2 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 p57^KIP gene failed to detect any mutations. Our data indicate: (a) infrequent genomic abnormalities at the p57^KIP2 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.

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