Feasibility of methylatedctDNAdetection in plasma samples of oropharyngeal squamous cell carcinoma patients

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de Jesus, Lais Machado ; dos Reis, Mariana Bisarro ; Carvalho, Raiany Santos ; Scapulatempo Neto, Cristovam ; de Almeida, Gisele Caravina ; Laus, Ana Carolina ; Marczynski, Gabriella Taques ; Leal, Leticia Ferro ; Melendez, Matias Eliseo ; de Marchi, Pedro ; Manuel Reis, Rui ; Carvalho, Andre Lopes ; de Carvalho, Ana Carolina

• Tipo de documento: Artigo Científico
• Fonte: HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK; v. 42, n. 11, p. 9-pg., 2020-07-20.

Resumo

Background Oropharyngeal squamous cell carcinomas (OpSCCs) are commonly associated with high rates of treatment failure. Objectives To evaluate methylation-based markers in plasma from OpSCC patients as emerging tools for accurate/noninvasive follow-up. Methods Pretreatment formalin-fixed paraffin-embedded (FFPE) biopsies (n = 52) and paired plasma (n = 15) were tested for the methylation ofCCNA1,DAPK,CDH8, andTIMP3by droplet digital PCR (ddPCR). Results Seventy-one percent (37/52) of the biopsies showed methylation of at least one of the evaluated genes and tumorCCNA1methylation was associated with recurrence-free survival. Methylated circulating tumor DNA (meth-ctDNA) was detected in 11/15 (73.3%) plasma samples; conversely, plasma samples from healthy controls were all negative for DNA methylation (area under the curve = 0.867; 95% confidence interval = 0.720-1.000). Additionally, preliminary results on the detection of meth-ctDNA in plasma collected during follow-up closely matched patient outcome. Conclusions The results suggest the feasibility of detecting meth-ctDNA in plasma using ddPCR and a possible application on routine setting after further validation. (AU)

• Processo FAPESP: 15/01286-0 - Caracterização de alterações genéticas e epigenéticas em genes específicos em tumores HPV-positivos e HPV-negativos de pacientes com carcinoma epidermóide de cabeça e pescoço
• Beneficiário: André Lopes Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/13834-7 - Comparação do perfil de metilação de genes específicos entre tumores HPV-positivos e HPV-negativos de pacientes com Carcinoma Epidermóide de Cabeça e Pescoço
• Beneficiário: Ana Carolina de Carvalho Peters
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/22658-9 - Detecção e caracterização de alterações moleculares em amostras de tecido e fluidos corpóreos de pacientes com câncer de cabeça e pescoço
• Beneficiário: Lais Machado de Jesus
• Modalidade de apoio: Bolsas no Brasil - Mestrado