REARRANJOS GÊNICOS EM TUMOR DE PARÓTIDA: PAPEL DAS FUSÕES PLAG1, HMGA2 E MAML2 NA ESTRATIFICAÇÃO DIAGNÓSTICA E PROGNÓSTICA
DOI:
https://doi.org/10.63330/aurumpub.034-018Palavras-chave:
Adenoma pleomórfico, Carcinoma mucoepidermoide, Fusões gênicas, Medicina de precisão, PrognósticoResumo
Os tumores de parótida apresentam ampla heterogeneidade morfológica e molecular, exigindo abordagens diagnósticas e prognósticas cada vez mais integradas. Este trabalho consistiu em uma revisão sistemática da literatura acerca do impacto dos rearranjos gênicos envolvendo PLAG1, HMGA2 e MAML2 na estratificação prognóstica das neoplasias salivares. A busca foi conduzida em bases de dados internacionais, priorizando estudos publicados entre 2021 e 2025, com critérios de inclusão voltados a investigações moleculares com correlação clínica e histopatológica. Os achados demonstraram que, no adenoma pleomórfico, as fusões envolvendo PLAG1 e HMGA2 atuam predominantemente como eventos iniciadores da tumorigênese, geralmente associados a comportamento benigno. Contudo, variantes específicas e alterações genéticas adicionais podem sinalizar risco de progressão para carcinoma ex-adenoma pleomórfico. No carcinoma mucoepidermoide, o rearranjo envolvendo MAML2 mostrou associação mais consistente com melhor prognóstico, incluindo menor taxa de recorrência e maior sobrevida global. A relevância clínica desses marcadores encontra respaldo na WHO Classification of Tumours, que incorpora critérios moleculares à classificação das neoplasias salivares. Conclui-se que o valor prognóstico das fusões gênicas é dependente do contexto histológico e molecular, devendo ser interpretado de forma integrada aos parâmetros clínicos e morfológicos. A consolidação da medicina de precisão nos tumores de parótida requer estudos prospectivos multicêntricos que validem modelos preditivos baseados em dados moleculares.
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AFSHARI, Mahsa; NEVADO, Pablo; FEHR, Andreas; HUANG, Jian; JÄWERT, Fredrik; NILSSON, Johan; STENMAN, Göran; ANDERSSON, Mattias. The transcriptomic and gene fusion landscape of pleomorphic salivary gland adenomas. Genes, Chromosomes & Cancer, v. 64, 2025.
AGAIMY, Abbas; IHRLER, Stephan; BANĚČKOVÁ, Michaela; MARTINEAU, Catherine; MANTSOPPOULOS, Konstantinos; HARTMANN, Arndt; IRO, Heinrich; STOEHR, Robert; SKALOVA, Alena. HMGA2-WIF1 rearrangements characterize a distinctive subset of salivary pleomorphic adenomas with prominent trabecular (canalicular adenoma-like) morphology. The American Journal of Surgical Pathology, v. 46, p. 190–199, 2021.
BARCA, Immacolata; MIGNOGNA, Carmela; DONATO, Giuseppina; CRISTOFARO, Maria. Expression of PLAG1, HMGA1 and HMGA2 in minor salivary glands tumours. Gland Surgery, v. 10, n. 5, p. 1609–1617, 2021.
BISHOP, Justin; THOMPSON, Lester; SIEGELE, Benjamin; GAGAN, Joshua; MANSOUR, Mark; CHERNOCK, Rebecca; ROOPER, Laura. Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2-rearranged salivary gland tumours. Histopathology, v. 82, 2022.
BUBOLA, Joseph; MACMILLAN, Christopher; DEMICCO, Edward; CHAMI, Rami; CHUNG, Catherine; LEONG, Ivan; MARRANO, Patricia; ONKAL, Zeynep; SWANSON, Daniel; VEREMIS, Basil; WEINREB, Ilan; ZHANG, Lei; ANTONESCU, Cristina; DICKSON, Brandon. Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors. Genes, Chromosomes & Cancer, v. 60, p. 695–708, 2021.
DE LIMA-SOUZA, Rafael; DE SOUZA VIEIRA, Gabriela; DE CARVALHO KIMURA, Thiago; SCARINI, Juliana; LAVAREZE, Letícia; FIGUEIREDO-MACIEL, Tatiana; GONÇALVES,
Marcelo; EGAL, Eduardo; ALTEMANI, Alfredo; MARIANO, Flávia. Insights into the molecular alterations of PLAG1 and HMGA2 in the malignant phenotype acquisition in pleomorphic adenoma. Critical Reviews in Oncology/Hematology, 2024.
EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY; EURACAN. Clinical practice guidelines: salivary gland cancer. 2024.
KAUR, Kanwal; MEHTA, Seema; VANIK, Shweta; TRIVEDI, Prakash; BANERJEE, Nandini; DHAR, Hena; DATTA, Sharmila; KARANJAI, Subrata. The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls. European Archives of Oto-Rhino-Laryngology, v. 279, p. 3769–3783, 2022.
KIM, Young; SONG, Jae; CHOI, Sung; NAM, Sang; CHO, Kyung. Association between the histological subtypes, anatomical locations, and MAML2 rearrangement of head and neck mucoepidermoid carcinoma. Head and Neck Pathology, v. 19, 2025.
MACAGNO, Nicolas; KERVARREC, Thomas; THANGUTURI, Sandeep; SOHIER, Pauline; PISSALOUX, David; MESCAM, Laurence; JULLIE, Marion; FROUIN, Emilie; OSIO, Antoine; FAISANT, Mathieu; LOARER, Laetitia; CRIBIER, Bertrand; CALONJE, Eduardo; LUNA, Elisa; MASSI, Daniela; GOTO, Kenji; NISHIDA, Hiroshi; PAINDAVOINE, Sophie; HOULIER, Aurore; TANTOT, Julien; BENZERDJEB, Nadia; TIRODE, Franck; DE LA FOUCHARDIÈRE, Anne; BATTISTELLA, Maxime. SOX10-internal tandem duplications and PLAG1 or HMGA2 fusions segregate eccrine-type and apocrine-type cutaneous mixed tumors. Modern Pathology, 2024.
MANSOUR, Bassem; DONATI, Marco; PANCSA, Tamas; GROSSMAN, Philip; ŠTEINER, Pavel; VANĚČEK, Tomas; COMOVÁ, Katerina; MICHAL, Michal; MICHAL, Michal. Molecular analysis of apocrine mixed tumors and cutaneous myoepitheliomas: a comparative study confirming a continuous spectrum of one entity with near-ubiquitous PLAG1 and rare mutually exclusive HMGA2 gene rearrangements. Virchows Archiv, v. 486, p. 215–223, 2024.
MIJARES, Kevin; WALD, Andrew; SEETHALA, Raja. YAP1::MAML2-rearranged poroid squamous cell carcinoma arising in a non-sebaceous lymphadenoma of the parotid gland. Head and Neck Pathology, v. 19, 2025.
OWOSHO, Adeyinka; ADESINA, Olufunke; ODUJOKO, Oluwatobi; AKINYEMI, Hakeem; KOMOLAFE, Akin; TADROS, Sherif; BAUER, Richard; SUMMERSGILL, Kimberley. HMGA2 immunoexpression is frequent in salivary gland pleomorphic adenoma: immunohistochemical and molecular analyses of PLAG1 and HMGA2 in 25 cases. International Journal of Clinical and Experimental Pathology, v. 15, n. 2, p. 63–71, 2022.
RIBEIRO, Eduardo; MALEKI, Zahra. Cystic salivary gland neoplasms: diagnostic approach with a focus on ancillary studies. Advances in Anatomic Pathology, 2022.
RUPP, Nina; HÖLLER, Stefan; BRADA, Markus; VITAL, David; MORAND, Gregory; BROGLIE, Marc; HUELLNER, Matthias; FREIBERGER, Stefan. Expanding the clinicopathological spectrum of TGFBR3-PLAG1 rearranged salivary gland neoplasms with myoepithelial differentiation including evidence of high-grade transformation. Genes, Chromosomes & Cancer, v. 61, p. 94–104, 2021.
STENMAN, Göran; FEHR, Andreas; SKALOVA, Alena; POORTEN, Vincent; HELLQUIST, Henrik; MIKKELSEN, Lars; SABA, Nabil; GUNTINAS-LICHIUS, Orlando; CHIESA-ESTOMBA,
Carlos; ANDERSSON, Mattias; FERLITO, Alfio. Chromosome translocations, gene fusions, and their molecular consequences in pleomorphic salivary gland adenomas. Biomedicines, v. 10, 2022.
TOPER, Mehmet; SARIOĞLU, Selim. Molecular pathology of salivary gland neoplasms: diagnostic, prognostic, and predictive perspective. Advances in Anatomic Pathology, 2021.
WANG, Shuang; ARANETA, Rina; KUWADA, Chihiro; GLOMSKI, Kevin. Potential diagnostic pitfall in pleomorphic adenoma: a case of squamous and mucinous metaplasia with MALAT1::PLAG1 fusion. Head and Neck Pathology, v. 19, 2025.
WHO CLASSIFICATION OF TUMOURS EDITORIAL BOARD. WHO classification of head and neck tumours. 5. ed. Lyon: IARC Press, 2022.
YOUSAF, Ahmad; SULONG, Siti; ABDULLAH, Baharudin; LAZIM, Nor. Heterogeneity of genetic landscapes in salivary gland tumors and their critical roles in current management. Medeniyet Medical Journal, v. 37, p. 194–202, 2022.
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