O gene PHF21B como candidato a predisposição familia em familial em cânceres de cabeça e pescoço
Carregando...
Data
2008-07-29
Autores
Bertonha, Fernanda Bernardi [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os carcinomas de células escamosas de cabeça e pescoço (CCECP) constituem 90% de todos os cânceres de cabeça e pescoço e estão associados a altas taxas de mortalidade, devido ao seu alto potencial infiltrativo. Este é o sexto tumor mais incidente na população Brasileira. Pouca atenção tem sido dada a fatores hereditários envolvidos em sua etiologia, mas estudos iniciais revelaram que os carcinomas orais tendem a se agregar em famílias. Evidências adicionais são fornecidas pela ocorrência de múltiplos tumores primários em pacientes com CCECP, pela associação com história familial, aparecimento precoce da doença e por membros afetados sem hábitos tabagista e etilista. Em estudos prévios do grupo foi descrita uma associação entre a perda de 22q e história familial de câncer em pacientes com CCECP, após análise citogenética, análise de LOH e PCR quantitativa em tempo real. O gene PHF21B (PHD finger protein 21B), mapeado em 22q13.31, codifica uma proteína reguladora transcricional e foi selecionado como um gene candidato associado a predisposição familial em CCECP. Os resultados da PCR quantitativa em tempo real mostraram associação estatisticamente significativa com relação à perda de seqüências do gene e história familial de câncer em parentes de 1º grau (P<0,0001). Estes dados sugerem que o PHF21B é um gene supressor tumoral candidato envolvido com história familial em carcinomas de cabeça e pescoço. Para investigar a inativação de um gene supressor tumoral (Knudson, 1971), foram selecionados 13 pacientes com CCECP que mostravam história familial positiva de câncer e outros 14 casos sem história familial. Foram considerados como critério para história familial positiva: parentes de primeiro e segundo graus com câncer; não-fumantes e não-consumidores de álcool; idade igual ou inferior a 56 anos quando do diagnóstico...
Head and neck squamous cell carcinomas (HNSCC) represents 90% of all cancers and are associated with high mortality, due to high infiltrative potential. This tumor is the sixth most incident in the Brazilian population. Little attention have been given to hereditary factors involved in their etiology, but early studies showed that oral carcinomas tend to aggregate themselves in families. Additional evidences are provided for primary multiple tumors occurrence in HNSCC patients, to family history association, early disease development and no tobacco and alcohol consumptions. Previously we described an association between 22q loss and cancer family history in HNSCC patients by cytogenetics, LOH and real time PCR analysis. The PHF21B gene (PHD finger protein 21B), mapped at 22q13.31, codifies a transcriptional regulatory protein and was selected as a putative gene associated with HNSCC familial predisposition. The real time PCR results showed statistical significant association related to gene loss and first degree family history (P<0,0001). This data suggests that PHF21B is a tumor suppressor gene candidate involved in HNSCC family history. To investigate the tumor suppressor gene inactivation (Knudson, 1971), were selected 13 HNSCC patients that had positive cancer family history and other 14 without HNSCC family history. It was considered for positive family history: first and second relatives with cancer; no tobacco and alcohol users; age 56 or less at diagnosis. Investigation analysis was performed by direct sequencing at exons: 7, 8 and 9. These exons were selected for its relation to PHD zinc-finger domain, responsible for PHF21B protein function. No mutations or significative variations were found in these exons. The SNPs (single nucleotide polymorphisms) analysis in gene extension showed a reduced SNPs number in exonic regions, however 16 SNPs were found at 3´UTR region... (Complete abstract click electronic access below)
Head and neck squamous cell carcinomas (HNSCC) represents 90% of all cancers and are associated with high mortality, due to high infiltrative potential. This tumor is the sixth most incident in the Brazilian population. Little attention have been given to hereditary factors involved in their etiology, but early studies showed that oral carcinomas tend to aggregate themselves in families. Additional evidences are provided for primary multiple tumors occurrence in HNSCC patients, to family history association, early disease development and no tobacco and alcohol consumptions. Previously we described an association between 22q loss and cancer family history in HNSCC patients by cytogenetics, LOH and real time PCR analysis. The PHF21B gene (PHD finger protein 21B), mapped at 22q13.31, codifies a transcriptional regulatory protein and was selected as a putative gene associated with HNSCC familial predisposition. The real time PCR results showed statistical significant association related to gene loss and first degree family history (P<0,0001). This data suggests that PHF21B is a tumor suppressor gene candidate involved in HNSCC family history. To investigate the tumor suppressor gene inactivation (Knudson, 1971), were selected 13 HNSCC patients that had positive cancer family history and other 14 without HNSCC family history. It was considered for positive family history: first and second relatives with cancer; no tobacco and alcohol users; age 56 or less at diagnosis. Investigation analysis was performed by direct sequencing at exons: 7, 8 and 9. These exons were selected for its relation to PHD zinc-finger domain, responsible for PHF21B protein function. No mutations or significative variations were found in these exons. The SNPs (single nucleotide polymorphisms) analysis in gene extension showed a reduced SNPs number in exonic regions, however 16 SNPs were found at 3´UTR region... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Genética, Cabeça - Tumores - Aspectos genéticos, Pescoço - Tumores - Aspectos genéticos
Como citar
BERTONHA, Fernanda Bernardi. O gene PHF21B como candidato a predisposição familia em familial em cânceres de cabeça e pescoço. 2008. 65 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências de Botucatu, 2008.