Recent studies have recognized a role for TNFRSF1A mutations in Multiple Sclerosis (MS).
As the title of Jaenisch's paper declared triumphantly, "One-step generatiof of mice carrying mutations in multiple genes".
Additionally, the related KMT NSD1 was recently discovered to harbor point mutations in multiple cancers, including HNSCC and AML (Dolnik et al., 2012; Yan et al., 2011).
Mice carrying mutations in multiple genes are traditionally generated by sequential recombination in embryonic stem cells and/or time-consuming intercrossing of mice with a single mutation.
Delhommeau and colleages then sequenced TET2 in patient tumor samples, becoming the first group to identify TET2 mutations in multiple myeloid neoplasms, including MDS (19%), MPNs (12%14%%), and sAML (24%).
Kandoth and colleagues characterized the presence of significant mutations in EMT-related genes and discovered mutations in multiple TGFβ-related pathways (Smad4: 2%; TGFBR2: 3%; ACVR1B: 1.3%; SMAD2: 1%; ACVR2A: 0.7% of the 301 HNC tumors sampled) [90].
Wang et al. simultaneously interrupted five distinct alleles in mouse embryonic stem cells, with an efficiency of 80%% to achieve the one-step generation of animals carrying mutations in multiple genes [1].
Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions.
Where once it was possible to test tumor samples for only one mutation or genomic rearrangement at a time, NGS technology now enables testing for multiple gene mutations in multiple samples simultaneously.
The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins.
As underscored by Wood et al. [2], colorectal cancer is the product of mutations in multiple genes operating simultaneously.
