Dados do Resumo

Título

Evaluation of Gene Fusions in Patients with Uterine Sarcomas and Applications in Clinical Practice.

Introdução

Uterine mesenchymal tumors are rare neoplasms, with diverse and heterogeneous presentations, which can often represent a diagnostic challenge, as many entities still lack defining histopathological characteristics. Therefore, the diagnosis of sarcomas is burdened with a high interobserver variability and misclassification rate. With the evolution of Next Generation Sequencing (NGS) techniques, numerous molecular alterations were discovered, particularly fusions, allowing the expansion of the classification of uterine tumors and making clear that the broad spectrum of sarcomas in this topography has not yet been fully characterized. Uterine sarcomas with NTRK rearrangements, characterized for the first time in 2018 by Chiang and colleagues, showed that, even though they are rare events, oncogenic fusions should be investigated in all patients with sarcoma for diagnostic and therapeutic purposes. Since then, many other fusions have been described as important biomarkers in uterine sarcomas, such as KAT6B/A::KANSL1, MEIS1::NCOA1/2, COL1A1::PDGFB, FGFR1::TACC1, YWHAE::NUTM2A/B, ZC3H7B:: BCOR, defining new entities. As there is a direct relation between histologic features and molecular characterization, we hypothesize that more fusions can be present and comprise specific subgroups of disease with their own characteristics.

Objetivo

The aim of this study is to characterize known and not yet described diagnostic entities within the scenario of uterine sarcomas. The main endpoint is to define new molecular biomarkers relevant to uterine sarcomas, allowing the development of appropriate therapeutic options that directly impact the survival of patients with this diagnosis.

Métodos

A comprehensive clinical, histopathologic and molecular study, including DNA methylation-based profiling and RNA-sequencing, will be carried out. After histopathologic review, a total of 100 cases, diagnosed as uterine sarcoma at the Department of Anatomic Pathology at A.C.Camargo Cancer Center (Sao Paulo – Brazil) from 2014 to 2023, were selected for DNA and RNA extraction for molecular study. Genomic DNA and RNA will be extracted from formalin-fixed, paraffin-embedded (FFPE) tissue sections. For the detection of gene fusions, the TruSight RNA Fusion Panel (Illumina, USA), an RNA-based NGS panel, with 507 genes implicated in cancer fusions, will be carried out. For the methylation profile, will be used the Infinium MethylationEPIC kit (Illumina, USA), according to the Infinium HD FFPE Methylation Assay (Illumina, USA) automated protocol, to obtain IDAT files. Morphological aspects, methylation classification, the CNV graph based on methylation, the position of the case on the t-SNE graph, as well as the results of the fusion panel carried out in parallel will be taken into account.

Resultados

The selected samples are in the DNA/RNA extraction phase. Sequencing is expected to begin next month.

Conclusões

It is expected that, with this comprehensive characterization, uterine sarcomas will be more adequately classified and that, in this way, better clinical outcomes will become a reality for patients with uterine malignant mesenchymal lesions.

Palavras Chave

Uterine; Sarcomas; Fusions