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      Loss of heterozygosity of APC and CDH1 genes in laryngeal squamous cell carcinoma.

      Pathology, research and practice
      Adult, Aged, Cadherins, genetics, Carcinoma, Squamous Cell, pathology, DNA, Neoplasm, analysis, Female, Genes, APC, Genetic Markers, Humans, Laryngeal Neoplasms, Loss of Heterozygosity, Male, Microsatellite Repeats, Middle Aged, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length

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          Abstract

          The molecular mechanisms involved in the development and progression of laryngeal cancer, specifically squamous cell carcinoma, still need further investigation and elucidation. Twenty-two laryngeal squamous cell carcinomas were analyzed in our study regarding genetic changes of two tumor suppressor genes: Adenomatous polyposis coli (APC) and E-cadherin (CDH1). APC gene instability was tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH) using the restriction fragment length polymorphism (RFLP) method. The samples were also screened for mutations using the heteroduplex method. E-cadherin gene was analyzed by PCR amplification of tetranucleotide marker (D16S752) linked to E-cadherin gene. The results of our analysis showed three samples with LOH of the APC gene out of 15 heterozygous patients (20%). Only one LOH of the CDH1 gene (5.5%) out of 18 heterozygous patients was discovered. D16S752 marker did not reveal any replication error-positive samples. There were six samples showing heteroduplexes (33%) encompassed in APC's exon 11. Altogether, nine samples (41%) showed alterations of the APC gene. Our results suggest that alterations of APC gene may have a role in squamous cell carcinoma development. Detected LOH of the E-cadherin gene indicates that genetic changes of this gene are not very frequent, but that other components of the wnt signaling cascade may also be involved.

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