Abstract
Cancer of unknown primary represents a heterogeneous group of malignancies characterised by early systemic dissemination and lack of primary site. KiSS1 is a member of the metastasis-suppressor gene family whose functional role is being investigated in human malignancies. We extracted DNA from 50 paraffin-embedded unknown primary tumors and screened KiSS1 exons III and IV for presence of mutations by means of Single Strand Conformational Polymorphism and direct sequencing. Only one tumor specimen harboured a cytosine to guanine point substitution in base 242 of exon IVa, resulting in a proline to arginine switch at codon 81 of the KiSS1 protein (P81R). The remaining 49 tumors harbored wild-type KiSS1 alleles, indistinguishable from those of peripheral blood lymphocytes of 50 healthy controls. Consequently, the propensity for systemic spread of unknown primary tumors may by due to mutations in genes other than KiSS1 or aberrant epigenetic regulation.
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