Polymerase chain reaction–based restriction fragment length polymorphism analysis of the short arm of chromosome 3 in primary head and neck squamous carcinoma

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Abstract
Deletion or loss of heterozygosity (LOH) at the polymorphic loci on the short arm of chromosome 3 has been reported in a large number of renal cell, small cell lung, non-small cell lung, and cervical carcinomas, suggesting the presence of one or more putative tumor suppressor genes at chromosome 3p. Similar studies in primary head and neck carcinoma are lacking. To investigate the possibility of chromosome 3p deletions, the authors applied a polymerase chain reaction (PCR)-based, restriction fragment length polymorphism analysis, in conjunction with conventional Southern blot techniques, to DNA samples of matched normal mucosa and head and neck squamous cell carcinomas from 18 patients. The authors also assessed the merit of the PCR-based assay as a rapid screening tool, particularly in assaying limited tissue samples. Constitutional heterozygosity at the polymorphic loci varied in the 18 normal samples that the authors studied: 12 at the D3F15S2 locus (on telomeric 3p21), 7 at the D3S32 locus (on centromeric 3p21), and 9 at the THRB locus (on 3p24). In 18 matched carcinoma specimens, LOH (deletion) was observed at D3S32 in 0 of 7, at D3F15S2 in 9 of 12 (75%), and at THRB in 3 of 9 cases (33%). The results of the PCR-based assay and Southern blotting were completely concordant in all specimens the authors studied. This study indicates that deletion at 3p is a frequent abnormality in primary head and neck carcinoma and that the most common deletion region is telomeric to D3S32. The authors also observed an apparent correlation among poor histologic differentiation, DNA aneuploidy, and 3p deletions. Most poorly and moderately differentiated and aneuploid carcinomas manifested the 3p deletion. Therefore, the authors suggest an association between deletion at 3p and aggressive biologic behavior.