TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells

Cancer arises from a single normal cell that undergoes further progression through sequential acquisition of various pathogenic mutations (depicted in Figure 1a). As next-generation sequencing technology becomes more affordable, the number of mutations identified in various cancers continues to increase. In fact, the most frequent mutations in all major cancers have now been mapped and cataloged.^{1, 2} Some of these mutated genes, for example, TP53, KRAS, BRAF, are well-known tumor suppressor genes or oncogenes, whereas the significance of mutations in other genes remains largely unknown. Although cancer is categorically clonal, tremendous subclonal heterogeneity is the unifying characteristic of all cancers due to prevalent mutation-driven clonal evolution.^{3, 4} In this post-genome sequencing era, the biggest question we are facing is how these mutations individually and in combination drive the initiation and progression of cancer.

TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells