Avaliação Genético-Molecular do Carcinoma das Células Escamosas da Laringe

• Ano de defesa: 2009
• Autor(a) principal: SILVA, Cláudio Carlos da
• Orientador(a): CRUZ, Aparecido Divino da
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Doutorado em Biologia
• Departamento: Ciencias Biologicas
• País: BR
• Palavras-chave em Português: p53; polimorfismo; LOH; MIS; câncer; laringe; CGH; 1.Biologia molecular 2.câncer 3.vias aéreas
• Palavras-chave em Inglês: p53; polymorphism, LOH; MIS, cancer, larynx, CGH
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tde/1009

The larynx is a structure of the upper aerodigestive tract responsible for the production of sounds as well as protecting the lower airways and helping during the normal act of swallowing. Any pathology which affects the larynx can impose several challenges that disrupt its normal physiological function, and consequently and directly resulting in reduction of the patient s quality of life. Among the different diseases that affect the larynx, cancer is one of the most serious. The squamous cell carcinoma (SCC) of the larynx is a multifactorial disease, influenced by environmental factors and individual behavioral, habits, and susceptibility. The current study describes the molecular and genetic assessment of 20 patients with the squamous cell carcinoma of the larynx. In summary, the study strategy included the analyses of the genetic polymorphism of codon 72 of the TP53, the detection and genotyping of HPV genome, assessing genomic instability (MIS and LOH) and random chromosomal imbalances using PCR and CGH approaches. Regarding to the polymorphism of the TP53 gene, arginine homozygous genotypes (p53AA) and arginine-proline heterozygous genotypes (p53PA) were found in 65% (13/20) and 35% (7 / 20) of cases, respectively. HPV genome was found in association with tumor cells in 20% of SCC cases. HPV 16, 11, and 45 were the genotypes identified. Moreover, co-infection of HPV 11 and 45 was also observed. Both samples found positive for HPV genome were associated with p53AA at the TP53 gene. Our results corroborated the data published in the literature that described an increased susceptibility to the virus-induced carcinogenesis of the larynx in arginine homozygous genotypes. Here in we report genomic instability for a panel of 8 microsatellite markers distributed in 5 chromosomes. One locus (D8S135) was found in homozygous for all cases. On the other hand, RH-92600 was not included in the analysis mainly because it was also found homozygous for most cases. We found 76.2% (244/320) of informative loci. Thus the mean frequency of MIS was 9.0% (22/244) and LOH was 6.1% (15/244). The frequency of MIS was found higher than the LOH, suggesting that the tumorigenesis of SCC of the larynx follows a mechanism of mutator phenotype. Using CGH, chromosomal gains were observed in 1q21qter. On the other hand, chromosomal losses occurred in chromosome 3p21p28, 11q23, 16p16, 16q12, 17p13pter and 22q13. The techniques of comparative genomic hybridization have improved the understanding of genetic alterations in squamous cell carcinoma of the larynx, especially for characterizing the relationship between early precursors of laryngeal carcinomas, as well as to identify genomic regions that may contain oncogenes and tumor suppressor genes involved in the tumorigenesis of this anatomical site.