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| Author(s): |
Anna Beatriz Machado Vercesi
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2022-08-19 |
| Examining board members: |
Tathiane Maistro Malta Pereira;
Sheila Coelho Soares Lima
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| Advisor: | Tathiane Maistro Malta Pereira |
| Abstract | |
Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) genes can be identified in different cancer types, such as gliomas and cholangiocarcinoma, and can correlate to changes in the DNA methylation levels in tumor cells, which results in the disruption of gene expression patterns via epigenetic mechanisms. The underlying modifications of these mechanisms are still not clear in most cases, remaining an important topic of investigation. We then propose, through the integrative analysis of DNA methylation and RNA expression data, to identify potential regulatory elements and transcriptional targets that can be associated with IDH mutations in tumor samples (IDHmut) compared to IDH wild-type samples of the same tumor types. We analyzed DNA methylation data from 3064 TCGA (The Cancer Genome Atlas) and 76 GEO (Gene Expression Omnibus) samples and RNA expression data from 2785 TCGA samples of 9 tumor types in which the occurrence of these mutations has already been identified, including low grade glioma (LGG), glioblastoma (GBM), cholangiocarcinoma (CHOL), skin cutaneous melanoma (SKCM), uterine corpus endometrial carcinoma (UCEC), acute myeloid leukemia (LAML), bladder urothelial carcinoma (BLCA), liver hepatocellular carcinoma (LIHC) and colon adenocarcinoma (COAD). The analyses were performed with open-source computational tools from R/Bioconductor. Our results showed that IDH mutant samples when compared to the IDH wild type group exhibit an RNA expression alteration and a hypermethylator profile, and these changes are more evident in some tumor types: CHOL, LAML, LIHC, and gliomas (LGG and GBM). However, these epigenetic alterations are different between the tumor types analyzed, which shows that other factors are also influencing these results. Additionally, through integrative analyses, we identified transcriptional targets that might be epigenetic regulated in association with IDH mutation, like the transcription factors SP1 and E2F7 (CHOL and gliomas, respectively) and M1TH and FLOT1 genes (CHOL and gliomas, respectively). (AU) | |
| FAPESP's process: | 20/05492-2 - Identification of regulatory regions associated with mutation in the IDH1/2 genes in different tumor types |
| Grantee: | Anna Beatriz Machado Vercesi |
| Support Opportunities: | Scholarships in Brazil - Master |