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.

大多数下一代测序（NGS）研究都鉴定出易患结直肠癌（CRC）的候选遗传变异体，但并未解决其功能解释以明确识别新的遗传性CRC基因的问题。此外，在尝试对具有重要意义的基因进行分类时，已经建立的遗传性CRC易感基因或体细胞变异中的种系变异具有相同的需求。功能基因组学方法在确定遗传结构与表型之间的因果关系方面具有重要作用，以破译健康和疾病中的细胞功能。因此，现在必须通过NGS平台对鉴定出的遗传变异进行功能解释。当今可用的方法包括生物信息学，细胞和分子生物学以及动物模型。最新进展，例如CRISPR-Cas9，ZFN和TALEN系统已被用作实现此目标的强大工具。但是，由于CRC异质性及其与微环境的紧密相互作用，因此细胞系的使用价值有限。模仿体内组织结构的三维培养物或类器官和异种移植模型的使用可能会彻底改变功能分析。这篇综述将侧重于最先进的功能研究的应用，以更好地解决与该肿瘤种系易感性有关的新基因。模仿体内组织结构的三维培养物或类器官和异种移植模型的使用可能会彻底改变功能分析。这篇综述将侧重于最先进的功能研究的应用，以更好地解决与该肿瘤种系易感性有关的新基因。模仿体内组织结构的三维培养物或类器官和异种移植模型的使用可能会彻底改变功能分析。这篇综述将侧重于最先进的功能研究的应用，以更好地解决与该肿瘤种系易感性有关的新基因。