Avaliação Genético-Molecular do Carcinoma das Células Escamosas da Laringe
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2009-10-21
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Universidade Federal de Goiás
Resumo
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.
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SILVA, Cláudio Carlos da. Assessing the Molecular and Genetic Aspects of Squamous Cell Carcinoma of the
Larynx. 2009. 220 f. Tese (Doutorado em Ciencias Biologicas) - Universidade Federal de Goiás, Goiânia, 2009.