Microsatellite Alterations at Chromosome 8q Loci in Pleomorphic Adenoma

Abstract

OBJECTIVE: To determine the extent, localization, and clinical significance of microsatellite loci alterations at sites of reported cytogenetic abnormalities in pleomorphic adenomas.

BACKGROUND: Pleomorphic adenoma is a benign salivary gland tumor with a propensity for recurrence and potential for malignant conversion. Although its cause remains unclear, clonal cytogenetic abnormalities have been reported consistently.

DESIGN: DNA extracted from paired normal and tumor tissue specimens from 1 patient with carcinoma ex pleomorphic adenoma and 17 patients with pleomorphic adenoma (3 contained foci of carcinoma ex pleomorphic adenoma) was evaluated for loss of heterozygosity at microsatellite loci with a multiplex polymerase chain reaction-based analysis. Correlation with clinical and pathologic features was performed.

RESULTS: Overall 10 (56%) of 18 cases manifested loss of heterozygosity at the loci tested. The frequency of loss of heterozygosity noted on 3p, 6q, 8p, 8q, and 12q microsatellite loci was 17%, 12%, 8%, 47%, and 27% of informative cases, respectively. Specimens from patients with carcinoma ex pleomorphic adenoma showed a similar loss of heterozygosity incidence at these loci. No apparent association between molecular abnormalities and clinical-pathologic features was observed in this cohort.

CONCLUSIONS: Loss of heterozygosity at microsatellite loci on 8q, a breakpoint at which translocations have been previously documented in pleomorphic adenoma, is a frequent event in this tumor. The incidence is not increased in patients with focal carcinoma ex pleomorphic adenoma, suggesting that loss of heterozygosity at 8q is an early event in tumorigenesis. Further evaluation at these loci is needed to identify potential tumor suppressor genes that may be associated with the initiation and progression of pleomorphic adenomas.

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