Sl. Lai et al., Loss of imprinting and genetic alterations of the cyclin-dependent kinase inhibitor p57(KIP2) gene in head and neck squamous cell carcinoma, CLIN CANC R, 6(8), 2000, pp. 3172-3176
The p57(KIP2) is a maternally expressed and paternally imprinted cyclin-dep
endent kinase inhibitor located on chromosome 11p15.5. Because of its locat
ion, biochemical functions, and imprinting status, p57(KIP2) has been consi
dered a candidate tumor suppressor gene. To determine, for the first time,
the involvement of this gene in the development of head and neck squamous c
arcinoma (HNSC), we analyzed the imprinting and expression status and loss
of heterozygosity (LOH),within the p57(KIP2) gene flanking loci on the 11p1
5.5 region in 64 primary untreated tumors. Of the 30 (47%) informative case
s for this gene, loss of imprinting and LOH were noted in 4 (13%) and 10 tu
mors (33%), respectively. Analysis of the microsatellite markers flanking t
he p57(KIP2) gene on chromosome 11p showed infrequent alterations at these
loci, p57KIP2 was expressed in all tumors with LOH within and around the ge
ne. Quantitative reverse transcription-PCR analysis showed elevated p57 mRN
A 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 indi
cate: (a) infrequent genomic abnormalities at the p57KIP2 gene in HNSC; (b)
leaky or incomplete imprinting of the paternal allele is associated with i
ncreased expression of this gene in a subset of tumors; and (c) minimal evi
dence for suppressor function for this gene in HNSC.