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Identification of somatic mutations in microRNA genes in colorectal tumor samples through next generation sequencing

Grant number: 13/04596-5
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2013
Effective date (End): May 31, 2015
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Raphael Bessa Parmigiani
Grantee:Bruna Paes de Barros
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Colorectal cancer is one of the malignant diseases most frequently found in the world and, although genetically it is one of the most studied tumor types, its treatment hasn't changed much in the last years. With the development of new sequencing technologies, it became possible to analyze the sequence from all known genes in the human genome. Recent studies showed that, in average, one colon tumor presents ninety mutations in coding regions. Today, a considerable attention is given to the important role of microRNAs on the control of gene expression in physiological and pathological conditions, including in cancer. Although many papers had described alterations in the expression pattern of these genes in different tumor types, curiously there is just one article describing the presence of somatic mutations in these genes. Despite they are non-coding genes, the way these RNAs perform their functions, combined with the way they are processed to form the mature molecule, indicates that mutations in these RNAs can be as deleterious as those found in coding genes, thus justifying a careful investigation of the occurrence of such event in cancer. Therefore, the present work aims to verify the occurrence of somatic mutations in miRNA genes in colorectal tumor samples, through next generation sequencing. The sequencing data will be analyzed and compared with the database of miRNA genes (miRBase) and, when necessary, with data from healthy colon of the same individual, to discard the occurrence of possible SNPs. Finally, if mutations were found, their impact on the expression of the mutated miRNA and its respective mRNA targets will be analyzed. Besides improving the understanding of tumor biology, the identification of these changes certainly could show new targets of more specific and effective therapy for the disease treatment.

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