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Distinct copy number signatures between residual benign and transformed areas of carcinoma ex pleomorphic adenoma

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Autor(es):
Scarini, Joao Figueira ; Sabino, Wellington Lima ; de Lima-Souza, Reydson Alcides ; Abu Egal, Erika Said ; Tincani, Alfio Jose ; Gondak, Rogerio ; Kowalski, Luiz Paulo ; Krepischi, Ana Cristina Victorino ; Altemani, Albina ; Mariano, Fernanda Viviane
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 14, n. 1, p. 10-pg., 2024-10-09.
Resumo

The mechanisms involved with the pathogenesis of carcinoma ex pleomorphic adenoma (CXPA) seem to be associated with the accumulation of molecular alterations in the pleomorphic adenoma (PA). In this sense, using array-based comparative genomic hybridization (aCGH) a rare series of 27 cases of CXPA and 14 residual PA (rPA) adjacent to the transformation area, we investigated the profile of the copy number alterations (CNAs) comparing benign residual and transformed areas. The main findings were correlated with the histopathological classification by histologic subtype and degree of invasion. The distribution of losses (p = 0.187) and amplifications (p = 0.172) was not statistically different between rPA and CXPA. The number of gains was increased in the transformed areas compared to the benign residual areas (p = 0.005). PLAG1 gain was maintained along the malignant transformation, as it was observed in both residual PA and CXPA samples, likely being an earlier event during transformation. The amplification of GRB7 and ERBB2 may also be an initial step in the malignant transformation of PA to CXPA (salivary duct carcinoma subtype). Furthermore, the amplification of HMGA2 and RPSAP52 were the most prevalent alterations among the studied samples. It was noteworthy that amplified genes in the transformed areas of the tumors were enriched for biological processes related to immune signaling. In conclusion, our results underscored for the first-time crucial CNAs in CXPA, some of them shared with the residual benign area adjacent to the transformation site. These CNAs included PLAG1 gain, as well as amplification of GRB7, ERBB2, HMGA2, and RPSAP52. (AU)

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: 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: 17/00831-0 - Estudo das alterações genéticase metabólicas do adenoma pleomorfo e carcinoma ex-adenoma pleomorfo por exoma, expressão gênica e imunohistoquímica
Beneficiário:Fernanda Viviane Mariano Brum Corrêa
Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
Processo FAPESP: 21/12567-1 - Validação de potenciais alterações genômicas encontradas durante a transformação maligna do adenoma pleomórfico
Beneficiário:João Figueira Scarini
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado