NUMERO: #20240897

Título: GENOMIC ALTERATIONS IN THE MALIGNANT TRANSFORMATION OF PLEOMORPHIC ADENOMA

Nome do Apresentador: Fernanda Viviane MARIANO

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Patologia Oral

Resumo: Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare and aggressive
tumor arising from the malignant transformation of pleomorphic adenoma (PA).
Objective: To identify genetic alterations driving CXPA development using whole
exome sequencing (WES) and array-based comparative genomic hybridization
(aCGH). Study Design: WES was performed on DNA samples from 7 PA, 13 CXPA,
and 5 residual PA, while aCGH was performed on FFPE samples from 27 CXPA
patients (and paired residual benign areas from 14 of them). Results: WES showed
that critical mutations were found in all groups, supporting a sequential PA-CXPA
transition in which genetic mutations drive phenotypic progression. aCGH confirmed
increased mutational events in CXPA compared to benign areas. Comparing aCGH
and WES results, 30% of genes affected by aCGH amplifications in CXPA were
mutated according to WES. However, only 13.2% of genes affected by aCGH
amplification in residual PA were mutated by WES. Mutated genes shared between
methods were enriched for immune signaling related processes and metalloproteinase
activity. Conclusions: In addition to mutations in important and well-known oncogenes
and tumor suppressor genes, our results highlight genes and processes related to the
tumor immune microenvironment and matrix remodeling, processes that remain
underexplored in the pathogenesis of these tumors.
FAPESP, grant numbers 15/07304-0, 19/09419-0,
and 21/12567-1. We thank the Brazilian Initiative on Precision Medicine (BIPMed) .

Autor 1:  Fernanda Viviane MARIANO

E-mail 1:  [email protected]

Autor 2:   João Figueira Scarini

E-mail 2:  [email protected]

Autor 3 :  Sheila Tiemi Nagamatsu

E-mail 3:  [email protected]

Autor 4:  Marcelo Falsarella Carazzolle

E-mail 4:  [email protected]

Autor 5:  Erika Said Abu Egal

E-mail 5:  [email protected]

Autor 6:  Rogério Moraes de Castilho

E-mail 6:  [email protected]

Autor 7:  Albina Altemani

E-mail 7:  [email protected]