| Texto completo | |
| Autor(es): Mostrar menos - |
de Lima-Souza, Reydson Alcides
;
Kimura, Talita de Carvalho
;
Scarini, Joao Figueira
;
Lavareze, Luccas
;
Maciel, Tayna Figueiredo
;
Damas, Ingrid Iara
;
Hara, Laura Wachter
;
Mesquita, Alessandra de Sousa
;
Simionato, Ana Valeria Colnaghi
;
Martinek, Petr
;
Michal, Michal
;
Kowalski, Luiz Paulo
;
Egal, Erika Said Abu
;
Altemani, Albina
;
Skalova, Alena
;
Mariano, Fernanda Viviane
Número total de Autores: 16
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Virchows Archiv; v. N/A, p. 13-pg., 2025-10-13. |
| Resumo | |
Pleomorphic adenoma (PA) is the most common salivary gland tumor. Although it is benign, PA may recur, metastasize, and undergo malignant transformation into carcinoma ex pleomorphic adenoma (CXPA). The mechanisms underlying this transformation are unclear, but it is believed that they involve the accumulation of molecular alterations. This study aimed to analyze the metabolomic profile associated with the acquisition of the malignant phenotype in PA and to identify the metabolic pathways involved in this process. A retrospective analysis was conducted using our institutional Salivary Gland Tumor Registry, which comprises 15 cases each of normal salivary gland (NSG), PA, recurrent PA (RPA), and CXPA. Metabolomic profiling was performed on formalin-fixed, paraffin-embedded tissue samples. Selected CXPA cases underwent genetic sequencing to investigate potential molecular alterations. The analysis revealed changes in carbohydrate, amino acid, and lipid metabolism. Notably, alterations in lipid-related pathways, particularly those involving fatty acids, appeared to play a significanat role in the acquisition of the malignant phenotype. Genetic analysis identified a novel NTF3::ITPR2 fusion in one CXPA case. Additionally, variants were detected in ARID1A, NSD1, XPO1, FOXA1, TP53, GATA2, LZTR1, PIK3CA, IRF4, and CHEK1, with allele frequencies ranging from 10% to 84%, indicating substantial genetic heterogeneity among CXPA cases. This study provides the first comprehensive metabolomic snapshot of malignant phenotype acquisition in PA. Identifying lipid metabolic dysregulation and a novel NTF3::ITPR2 gene fusion highlights potential diagnostic biomarkers and unveils actionable pathways that could be translated into targeted and personalized therapies for salivary gland tumors. (AU) | |
| Processo FAPESP: | 23/13091-6 - AVALIAÇÃO DA EXPRESSÃO DE miRNAs E POTENCIAIS ALVOS NA TRANSFORMAÇÃO MALIGNA DO ADENOMA PLEOMÓRFICO |
| Beneficiário: | Talita de Carvalho Kimura |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 19/09419-0 - Alterações genômicas na transformação maligna do Adenoma Pleomorfo |
| Beneficiário: | João Figueira Scarini |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 23/01150-8 - Desvendando o papel das alterações metabolômicas associadas com a aquisição do fenótipo maligno no adenoma pleomórfico |
| Beneficiário: | Reydson Alcides de Lima Souza |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |
| Processo FAPESP: | 22/11861-6 - Análise comparativa de exoma de Carcinoma Adenóide Cístico em modelo de xenoenxerto com e sem terapia com entinostat e cisplatina |
| Beneficiário: | Luccas Lavareze dos Reis |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 15/07304-0 - Estudo das alterações genéticas e metabólicas do adenoma pleomorfo e carcinoma ex-adenoma pleomorfo por exoma, expressão gênica e imunohistoquímica |
| Beneficiário: | Fernanda Viviane Mariano Brum Corrêa |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 20/08431-4 - Análise do perfil metabolômico na transformação maligna do adenoma pleomórfico |
| Beneficiário: | Reydson Alcides de Lima Souza |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |