Insights into the molecular alterations of PLAG1 and HMGA2 associated with malignant phenotype acquisition in pleomorphic adenoma

Author(s)

Lima-Souza, Reydson Alcides de ; Vieira, Gustavo de Souza ; Kimura, Talita de Carvalho ; Scarini, Joao Figueira ; Lavareze, Luccas ; Maciel, Tayna Figueiredo ; Goncalves, Moises Willian Aparecido ; Abu Egal, Erika Said ; Altemani, Albina ; Mariano, Fernanda Viviane

• Document type: Journal article
• Source: CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY; v. 204, p. 10-pg., 2024-10-04.

Abstract

Pleomorphic adenoma (PA) is the most common neoplasm of the salivary gland, presenting with a variety of histological features. In some cases, PA can undergo malignant transformation to carcinoma ex pleomorphic adenoma (CXPA). The transition from PA to CXPA is associated with complex molecular alterations, particularly involving the pleomorphic adenoma gene 1 (PLAG1) and high mobility group protein gene (HMGA2). This review investigates the molecular alterations of PLAG1 and HMGA2 in all domains in the malignant transformation of PA. Our analysis highlights that these markers are key alterations in the etiopathogenesis of PA and CXPA, with gene fusion and amplification being frequently reported mechanisms. Although the exact role of PLAG1 and HMGA2 in the oncogenic process remains unclear, further studies on the HMGA2 and PLAG1, are needed particularly in HMGA2-PLAG1-IGF2 which is proving to be a potential pathway for the development of clinically applicable therapies, especially for CXPA management. (AU)

• FAPESP's process: 19/09419-0 - Genomic alterations in the malignant transformation of the Pleomorphic Adenoma
• Grantee: João Figueira Scarini
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 23/13091-6 - ANALYSIS OF miRNAs EXPRESSION AND POTENTIAL TARGETS IN THE MALIGNANT TRANSFORMATION OF PLEOMORPHIC ADENOMA
• Grantee: Talita de Carvalho Kimura
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/07304-0 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry
• Grantee: Fernanda Viviane Mariano Brum Corrêa
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 22/07410-9 - COMPARATIVE PROTEOGENOMIC ANALYSIS BETWEEN BENIGN SALIVARY GLAND NEOPLASMS SHOWING MYOEPITHELIAL DIFFERENTIATION
• Grantee: Gustavo de Souza Vieira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/08431-4 - METABOLOMIC PROFILING ANALYSIS IN THE MALIGNANT TRANSFORMATION OF PLEOMORPHIC ADENOMA
• Grantee: Reydson Alcides de Lima Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/11861-6 - Comparative analysis of Adenoid Cystic Carcinoma exome in xenograft model with and without entinostat and cisplatin therapy
• Grantee: Luccas Lavareze dos Reis
• Support Opportunities: Scholarships in Brazil - Doctorate