Actionable genomic alterations

Hotspot mutations have been identified with cancer hotspot database (http://cancerhotspots.org)^{26, 75} using protein change annotation retrieved from TransVar⁷³.

Cancer hotspot tool provides useful resources for query and visualization of statistically significant hotspot mutations among diverse tumors. Then, to determine the clinical actionability and oncogenicity of identified mutations, OncoKB²⁷ knowledgebase was interrogated. OncoKB provides disease-specific levels of evidence for the actionability of mutant alleles and DNA copy-number alterations as follows: (1) level 1 alteration is an FDA-recognized biomarker in specific tumor type; (2) level 2 is a biomarker routinely used to guide prescribing of an FDA-approved drug, based on tumor type (2A) or other indication (2B); (3) level 3 demonstrates compelling clinical evidence supporting its use as a biomarker. OncoKb also categorized a specific gene as “oncogenic” or “likely oncogenic” in accordance with its alterations and biological consequence.