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Author
Gonfaus Otiz, Gemma
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Abstract
Colorectal cancer (CRC) is currently one of the most common neoplasms in developed countries and represents the second deadliest cancer after lung cancer. This neoplasm develops from different precursor lesions that include conventional adenomas and serrated polyps in the colon. Although most CRCs progress through the adenoma-carcinoma pathway, serrated polyps are also considered precursor lesions of the CRC.
Serrated polyposis syndrome (SPS) is a condition characterized by the development of large, multiple serrated polyps throughout the colon, which poses a greater risk of developing CRC. The prevalence of CRC in patients with SPS has been estimated to be between 15% and 35%. Despite the latest developments in sequencing technologies, the genetic etiology of SPS remains largely unknown. The aim of the project is based on the characterization of 3 genetic variants (detected in 2 cohorts of patients) of the hypermethylated in cancer 1 (HIC1) gene, which is a tumor suppressor, to determine if they are pathogenic and involved in predisposition to SPS.
In order to evaluate these 3 variants, HIC1 functional knockout (KO) cells are generated using the CRISPR/Cas9 technique, the variants are synthesized by PCR and introduced into KO cells by lentiviral infection. In this way, the pathogenicity of candidate variants can be evaluated. The aim of this work is the generation of these variants for HIC1 and the definitive validation of the KOs generated in the laboratory previously at both RNA and protein levels.
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