Recent advances in next generation sequencing technologies have enabled comprehensive cancer genomic testing by molecular pathologists across multiple tumor types. However, it is often challenging to assign the clinical and biological relevance of specific mutations observed in patients. While there is a multitude of databases that provide in silico assessment, there is no comprehensive database for annotating driver and passenger mutations.
Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists and laboratory directors to facilitate literature-based annotation of genomic testing of tumors. We curated the chromosome location, all possible nucleotide positions, for each amino acid change and uploaded them to the CanDL database with associated literature reference.
Rules for mutational entry into CanDL
Listed below are the rules for mutational entry into the CanDL (Cancer Driver Log) database:
- Targeted clinically or in vitro with approved or investigational agent(s)
- Associated with increased sensitivity to a drug in vitro or in vivo
- Associated with resistance to a drug in vitro or in vivo
- Ectopic expression induces transformation in vitro (e.g. BAF3, NIH 3T3 cells) or in vivo (e.g. animal models)
- Inhibition of the mutant with a specific shRNA or an inhibitor decreases cell growth
Level of Evidence
Entries are classified into four (4) tiers by level of evidence:
- Alteration has matching FDA approved or NCCN recommended therapy.
- Alteration has matching therapy based on evidence from clinical trials, case reports, or exceptional responders.
- Alteration predicts for response or resistance to therapy based on evidence from pre-clinical data (in vitro or in vivo models).
- Alteration is a putative oncogenic driver based on functional activation of a pathway.
Development and Maintenance
The Roychowdhury Lab Team at The Ohio State University has developed this internal research resource for identifying literature evidence of driver mutations in cancer, and our goal is to share this information broadly for other translational cancer researchers to use.
The current version number is 1.1 - Mar2015. The most recent update to data was on 5:15pm, July 31st, 2015.