Full text
| |
| Author(s): |
Leonardo Tomiatti da Costa
Total Authors: 1
|
| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2018-03-29 |
| Examining board members: |
Kátia Cândido Carvalho;
Edmund Chada Baracat;
Dirce Maria Carraro
|
| Advisor: | Kátia Cândido Carvalho |
| Abstract | |
Uterine sarcomas are rare mesodermal tumors that comprise about 3% of all cancers in this organ. They present histological diversity, aggressive behavior, early dissemination and high mortality rates. Recently, carcinosarcomas (CCS) were histological reclassified as carcinomas. Here, we have included them in our series for purposes of comparison of the mesenchymal component and also because these tumors still form part of both the majority of studies and the WHO\'s latest classification for uterine sarcomas (Word Health Organization). Because of their diversity and rarity, there is no consensus regarding the risk factors for poor prognosis and appropriate treatment for these tumors. Thus, information about their gene and protein profiles can help in the diagnosis and prognosis of these tumors, as well as in the understanding of their biology and clinical behavior. We performed the New Generation Sequencing of 14 samples of uterine sarcomas (5 CCS, 4 LMS, 4 SEE and 1 ADS, using the Ion Proton System platform (ThermoFisher).) Among the 14 samples, we found 27 LoF (loss of gene function) and 40 missense mutations, with a mean of 39 insertions and 52 deletions per sample, totaling 70 mutations, 25 described in the COSMIC database. The most commonly mutated genes in our sample were TP53 (50%), KMT2D (36%), ATM (29%), DICER1 (21%), PIK3CA (21%), TRRAP (21%).Our main objective was to find specific mutations for each histological subtype, but only SEEs (PDE4DIP) and CCS (ERBB4 and PIK3CA) had specific mutations. In another analysis, we observed that all the histological subtypes share the KMT2D gene, which will be studied in future analyzes. Others analyzes, using a custom panel, are necessary to understand these mutations and its biological implication in uterine carcinosarcoma and sarcomas (AU) | |
| FAPESP's process: | 16/03163-6 - Study of gene alterations in samples of uterine sarcomas and uterine carcinosarcomas: Identification of markers for differential diagnosis and treatment |
| Grantee: | Leonardo Tomiatti da Costa |
| Support Opportunities: | Scholarships in Brazil - Master |