Figure 3 from Coevolution of Atypical <i>BRAF</i> and <i>KRAS</i> Mutations in Colorectal Tumorigenesis
Woolley CE., Domingo E., Fernandez-Tajes J., Pennel KAF., Roxburgh P., Edwards J., Richman SD., Maughan TS., Kerr DJ., Soriano I., Tomlinson IPM.
<p>Classes of <i>BRAF</i> mutation exhibit distinct clinicopathologic and molecular characteristics. <b>A,</b> Subdivision of the large bowel into the proximal and distal colorectum. Proportions of colorectal cancers in each location are shown by <i>BRAF</i> mutation class. <b>B,</b> CMS classifications of <i>BRAF</i>-mutant colorectal cancers by mutation class. The differences between class 2 or 3 versus class 1 (V600E) were highly significant (<i>P</i> < 0.001). No significant difference was observed between classes 2 and 3 (<i>P</i> = 0.270). <b>C</b> and <b>D,</b> Sanger sequencing chromatograms highlighting the spatial co-occurrence of <i>BRAF</i> and additional Ras pathway mutations in two colorectal cancers. Two regions of each cancer were microdissected, DNA was extracted, and relevant exons were PCR-amplified prior to Sanger sequencing. Illustrative results are shown. The co-occurrence of <i>BRAF</i><sup>G466V</sup> and <i>NRAS</i><sup>G12D</sup> can be observed in tumor 1 (<b>C</b>), and of <i>BRAF</i><sup>D594G</sup> and <i>KRAS</i><sup>L19F</sup> in tumor 2 (<b>D</b>). This analysis does not exclude fine-scale spatial mixing of distinct subclones but is consistent with the two mutations tested being present in the same tumor cells. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.)</p>