Next Generation Sequencing in Pediatric Adrenocortical Tumors

Abstract

Genetic abnormalities underlie the formation and progression of most tumors in humans, including pediatric adrenocortical tumors. There is increasing evidence that gene interaction and interaction networks between genes and proteins play a key role in tumorigenesis processes. New generation sequencing (NGS) is the most promising technology for detecting new mutations. This technology is able to generate huge amount of information. Theoretically, all mutations, regardless of variant allelic frequency (VAF) or genomic region, can be observed with adequate reading depth in the NGS process. However, recording them (reliably) with confidence is not a trivial task because of the noise introduced by the readings. Numerous bioinformatics tools have been developed to discover mutations (variants) from NGS reads (readings).Bioinformatics of tumors is one of the multiple ways of concentrating bioinformatics methods in this context, seeking to understand the specificity of disease metabolism, signaling, communication and cell proliferation. Clinical bioinformatics, an emerging science that combines clinical informatics, bioinformatics, information technology, mathematics, and proteomic sciences, can be considered one of the critical elements that address relevant clinical challenges in early diagnosis, effective therapies, and predictive and prognostic methods for cancer patients.Perspectives: The integrated use of bioinformatics tools in the data generated by the NGS of adrenocortical tumors, one of the subprojects of the Thematic Project to which this fellowship will be linked, will generate important information about the occurrence of genetic variations in these tumors (somatic damage) and the alterations predisposing variants (germline). These results could allow the reclassification of these tumors based on their genetic profile, detect new prognostic markers, and detect new cellular pathways involved in tumorigenesis and with potential to open the possibility for new functional studies and the search for new specific therapeutic agents.The four main objectives of the present post-doctoral project are, by means of bioinformatics analysis to:1 - Detect somatic and germline changes (SNPs, indels, CUV, Svs) in tumor DNA and genomic DNA samples from patients with pediatric adrenocortical tumors.2 - Identify previously described changes and verification of new changes.3 - Compare with international bases of variants for identification of Brazilian signatures in the data set.4 - Evaluate the association between distinctions found, tumor phenotype and clinical outcome.