Many labs struggle with prioritizing clinically- and biologically-relevant variants among the millions of variants detected using NGS. Labs are starting to consolidate smaller panels into one large comprehensive cancer panel to test all cancer types. This presents fresh challenges: interpretation of the data and meeting turnaround times.
Fortunately, with COSMIC’s Cancer Mutation Census and Actionability, labs have the trusted data they need for accurate prioritization at their fingertips.
COSMIC’s Cancer Mutation Census (CMC)
CMC delivers a score for each variant based on manually-curated information regarding cancer genes and genetic variants. It also provides data on variant frequencies in cancer and non-cancer populations. It utilizes data from many reliable sources, including ClinVar, gnomAD, DNA conservation as reported by GERP, and COSMIC Mutations per AA.
CMC’s algorithmic evaluation of variant significance across the whole set of coding mutations in COSMIC lets you identify variants with the highest potential of biological relevance. The latest version of CMC—v96—describes over 4.9 million somatic variants. It segregates them into four tiers (see Figure 1, below) in order of highest confidence and evidence of driving cancer (Tier 1) to the lowest (Tier 4).
During your NGS data analysis, you can easily match the CMC score to the identified mutations in your NGS test using genomic coordinates, cDNA, or protein change. This lets you rank the mutations in your NGS data according to the CMC score—prioritizing potential biological cancer-driving mutations.
Figure 1. CMC tiers allow you to rapidly classify somatic variants by their potential to drive cancer.
COSMIC Actionability delivers the latest data on the availability and development of drugs targeting specific somatic mutations in cancer. Actionability covers clinically-relevant mutations and alteration types in relevant genes for some of the most frequently sequenced cancer types such as lung, breast, melanoma, ovarian, and colon cancer. This data is updated quarterly; for more information on the latest Actionability release, see below.
With Actionability, you can prioritize clinically-actionable mutations related to your patient’s specific cancer type. This lets you know which of those potentially biologically-relevant mutations are also therapeutically actionable.
Like CMC, Actionability also classifies alterations into four tiers:
- Tier 1: Contains alteration types associated with approved drugs and demonstrated efficacy.
- Tier 2: Covers alterations associated with drugs described in clinical phase 2/3 studies that met its primary outcome measure with a p-value statistic £0.05 or has been described as meeting trial objectives in associated publications.
- Tier 3: Alterations that are of potential clinical significance if tested in ongoing clinical trials.
- Tier 4: Alterations that have been described in case studies.
Actionability currently covers 62 tier 1, 21 tier 2, 527 tier 3, and 91 tier 4 alterations and alteration types, including those associated with the most common tumor profiling biomarkers and cancer types (see Table 1, below).
Table 1. Genes and cancer types currently included in Actionability data. List of genes adapted from Illumina’s TSO500 tumor profiling biomarkers for multiple cancer types . Note: some genes are not yet fully curated, but have been prioritized for curation in Actionability V7 (tentatively launching October 2022).
CMC and Actionability help you rank biologically and clinically relevant mutations easily and efficiently. With the complete set of COSMIC downloadable files, you can further refine the priorities of relevant mutations with the mutational frequency in your patient’s cancer type, as well as resistance mutations.
The latest COSMIC Actionability release is here!
COSMIC Actionability is updated with new content every quarter. The latest release, V6, contains the following:
- Updates to trial statuses, patient numbers, results availability and estimated or actual primary completion dates
- An increase in the number of drugs covered from 1278 to 1408
- Nine new fully curated genes
See the complete release statistics in Figure 2, below.
Figure 2. COSMIC Actionability V6 release statistics.
Want to know more about COSMIC?
Learn more about COSMIC and how the industry-leading database can help you identify biomarkers, annotate variants, and explore the etiology of human cancers here.
Download COSMIC sample data
See first-hand how COSMIC can be used in your lab and the quality of the database’s content by downloading sample data here.
- Illumina. TruSight™ Oncology 500: data sheet. 2022; 3: 3. https://www.illumina.com/content/dam/illumina/gcs/assembled-assets/marketing-literature/trusight-oncology-500-data-sheet-m-gl-00173/trusight-oncology-500-and-ht-data-sheet-m-gl-00173.pdf.