FIG 1.

Genomic profiling results from pancreatic tumors harboring RAF pathway alterations. (A) Lollipop plot highlighting amino acid positions along the BRAF gene where alterations were most commonly found in this case series (n = 81). Each stemmed circle represents the numbers of patients with a BRAF alteration at each position (or type for structural variants), counted separately on the basis of either the presence (downward lollipop) or absence (upward lollipop) of a confounding alteration in another oncogenic driver (eg, KRAS mutation). RAF-altered molecular profiles were categorized into four subgroups that have been associated with distinct implications for therapy: Exon 15 (blue; V600 mutations that have been associated with responsiveness to canonical BRAF inhibitors), Exon 11 (red; non-V600 mutations that confer RAS-independent activity but are likely vemurafenib-insensitive), Fusions (teal; intergenic structural variants), and Other (orange; structural and/or short variants, either uncharacterized, characterized as RAS-dependent mutations, or found alongside confounding driver mutations). The three most common variants (BRAF V600E, BRAF N486_P490del also known as ΔNVTAP, and SND1-BRAF fusions) are highlighted at three hotspots that form the basis for the subgroups. (B) Molecular matrix organized by RAF subgroup shows genomic testing results for each patient including specific BRAF variants, RAF fusions, confounding drivers, and p53/CDKN2A/SMAD4 mutations.