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

• Published in: Critical reviews in oncology/hematology 2024-12, Vol.204, p.104494, Article 104494
• Main Authors: de Lima-Souza, Reydson Alcides, Vieira, Gustavo de Souza, Kimura, Talita de Carvalho, Scarini, João Figueira, Lavareze, Luccas, Maciel, Tayná Figueiredo, Gonçalves, Moisés Willian Aparecido, Egal, Erika Said Abu, Altemani, Albina, Mariano, Fernanda Viviane
• Format: Article
• Language: English
• Subjects: Adenoma, Pleomorphic - genetics; Adenoma, Pleomorphic - metabolism; Adenoma, Pleomorphic - pathology; Carcinoma ex pleomorphic adenoma; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; HMGA2; HMGA2 Protein - genetics; HMGA2 Protein - metabolism; Humans; Molecular profile; Phenotype; PLAG1; Pleomorphic adenoma; Salivary gland neoplasm; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - metabolism; Salivary Gland Neoplasms - pathology
• ISSN: 1040-8428; 1879-0461; 1879-0461
• DOI: 10.1016/j.critrevonc.2024.104494

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. •PLAG1 and HMGA2 are the main mutational targets in the etiopathogenesis of PA and CXPA, with gene fusions frequently reported.•PLAG1 and HMGA2 have been used as diagnostic markers for PA and CXPA, even when histologic features suggest otherwise.•Investigation of the HMGA2-PLAG1-IGF2 pathway may lead to the development of clinically applicable therapies for PA and CXPA.