Approaches to functionally validate candidate genetic variants involved in colorectal cancer predisposition
Year: 2019
Type: review
Abstract: Most next generation sequencing (NGS) studies identified candidate genetic variants predisposing to colorectal cancer (CRC) but do not tackle its functional interpretation to unequivocally recognize a new hereditary CRC gene. Besides, germline variants in already established hereditary CRC-predisposing genes or somatic variants share the same need when trying to categorize those with relevant significance. Functional genomics approaches have an important role in identifying the causal links between genetic architecture and phenotypes, in order to decipher cellular function in health and disease. Therefore, functional interpretation of identified genetic variants by NGS platforms is now essential. Available approaches nowadays include bioinformatics, cell and molecular biology and animal models. Recent advances, such as the CRISPR-Cas9, ZFN and TALEN systems, have been already used as a powerful tool with this objective. However, the use of cell lines is of limited value due to the CRC heterogeneity and its close interaction with microenvironment. Access to tridimensional cultures or organoids and xenograft models that mimic the in vivo tissue architecture could revolutionize functional analysis. This review will focus on the application of state-of-the-art functional studies to better tackle new genes involved in germline predisposition to this neoplasm.
Source: Molecular Aspects of Medicine
Institutions: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Centro de Investigación Biomédica en Red de Cáncer, Legacy Health, Sabancı Üniversitesi, Hospital Clínic de Barcelona
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,150
Funders: Centres de Recerca de Catalunya, European Cooperation in Science and Technology, Centro para el Desarrollo Tecnológico Industrial, Fundación Científica Asociación Española Contra el Cáncer, Generalitat de Catalunya, Federación Española de Enfermedades Raras, Ministerio de Economía y Competitividad, Centro de Investigación Biomédica en Red de Cáncer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund
Awards: G1599727553, G1799271136, G2116329792, G2312245233, G2813111952, G2816175284, G3288897321, Caracterización funcional de variantes en nuevos genes candidatos en la predisposición germinal al cáncer colorrectal y el síndrome de poliposis serrada (FUNCTION4GENE), G4016371942, G4509608868, G4582569229, G4583745634, G5101934552, G5312756924, G5507745976, G5554424168, G56649681, G5716082512, G5801982654, G6221370081, G629507414, G6692840757, G6903488607, G6930650830, G7814476630, G8468341081, G8644963432, G8698840131, G972838295
OpenAlex ID: W2929763044