Association of Inherited Copy Number Variation in ADAM3A and ADAM5 Pseudogenes with Oropharynx Cancer Risk and Outcome

Autor(es)

Carron, Juliana ; Torricelli, Caroline ; Silva, Janet Keller ; Liu, Yichuan ; Pellegrino, Renata ; Passos Lima, Carmen Silvia ; Lourenco, Gustavo Jacob

• Tipo de documento: Artigo Científico
• Fonte: GENES; v. 13, n. 12, p. 13-pg., 2022-12-01.

Resumo

Inherited copy number variations (CNVs) can provide valuable information for cancer susceptibility and prognosis. However, their association with oropharynx squamous cell carcinoma (OPSCC) is still poorly studied. Using microarrays analysis, we identified three inherited CNVs associated with OPSCC risk, of which one was validated in 152 OPSCC patients and 155 controls and related to pseudogene-microRNA-mRNA interaction. Individuals with three or more copies of ADAM3A and ADAM5 pseudogenes (8p11.22 chromosome region) were under 6.49-fold increased risk of OPSCC. ADAM5 shared a highly homologous sequence with the ADAM9 3 '-UTR, predicted to be a binding site for miR-122b-5p. Individuals carrying more than three copies of ADAM3A and ADAM5 presented higher ADAM9 expression levels. Moreover, patients with total deletion or one copy of pseudogenes and with higher expression of miR-122b-5p presented worse prognoses. Our data suggest, for the first time, that ADAM3A and ADAM5 pseudogene-inherited CNV could modulate OPSCC occurrence and prognosis, possibly through the interaction of ADAM5 pseudogene transcript, miR-122b-5p, and ADAM9. (AU)

• Processo FAPESP: 06/06231-0 - Identificacao de genes de susceptibilidade para o carcinoma de celulas escamosas de orofaringe por genotipagem em larga escala.
• Beneficiário: Gustavo Jacob Lourenço
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/17182-1 - Análise da expressão de genes polimórficos identificados em portadores de carcinoma de células escamosas de base de língua
• Beneficiário: Gustavo Jacob Lourenço
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/07054-5 - Identificacao de genes de susceptibilidade para o carcinoma de celulas escamosas de orofaringe por genotipagem em larga escala.
• Beneficiário: Carmen Silvia Passos Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular