COSMIC v101 and Actionability v14: Insights into rare cancers and actionable targets

New data has been added to the Catalogue of Somatic Mutations in Cancer (COSMIC), with the availability of the COSMIC v101 and Actionability v14 releases. These updates enhance our understanding of somatic mutations across rare and high-need cancers while expanding actionable insights for clinical applications.

In this article, we provide a summary of the COSMIC v101 and Actionability v14 release highlights.

What is COSMIC?

COSMIC is an expert-curated database encompassing the wide variety of somatic mutation mechanisms causing human cancer. Owned and maintained by the Wellcome Sanger Institute, COSMIC is exclusively licensed through QIAGEN.

COSMIC’s team of variant scientists manually curates key cancer genes to provide in-depth information on mutation distributions and effects. The team relies on a semi-automated curation process of cancer genomes to provide broad somatic annotations toward target discovery and identification of patterns and signatures. To date, COSMIC contains over 24 million somatic mutations associated with more than 6,800 human cancers.

COSMIC v101 release highlights

Key Curation Focus
The v101 release prioritizes somatic mutation data from whole genome sequencing (WGS) and whole exome sequencing (WES) studies, emphasizing rare cancer types and cancers with high medical need. Key areas of focus include:

• Female-specific cancers: Expanding mutation profiles for these critical condition
• Paediatric cancers: Such as neuroblastoma and retinoblastoma.
• Endocrine tumours: Across multiple organs.
  

Highlight: Chernobyl Radiation and Papillary Thyroid Cancer

Among the curated studies, a systematic screen (PMID: 33888599) analyzing radiation-related genomic alterations in papillary thyroid cancer (PTC) provides significant insights. The study analyzed 383 samples, 305 from individuals exposed as children to ionizing radiation from the 1986 Chernobyl disaster. Key findings include:

• Mutation data: 318,907 somatic mutations identified, comprising 315,022 non-coding and 3,885 coding variants.
• Common mutations: The BRAF V600E mutation was the most frequent (45.2%), followed by mutations in the RAS family (NRAS, HRAS, and KRAS).
• Driver events: While most cases were driven by mutations (59%), others were driven by fusions, which were more prevalent in individuals exposed to higher radiation levels or diagnosed at a younger age.
• Mechanisms: Tumorigenesis appears linked to DNA double-strand breaks, impacting thyroid cell growth and differentiation.

This contrasts findings from the Fukushima nuclear accident, where BRAF V600E mutations predominated, mirroring patterns in sporadic PTC (PMIDs: 26584635, 32827026).

Additional updates in COSMIC v101

• New Hallmarks of Cancer Annotations: Eight genes (e.g., BAX, IKZF3, SOX2) now include hallmark annotations.
• Cancer Mutation Census (CMC) Updates: Corrected assignment of mutational significance for the v100 release and alignment with the v101 update ensure accurate tier categorization.

→ Want more details? Read the full COSMIC v101 release notes for more details.

What is COSMIC Actionability?

COSMIC Actionability is a standalone product within the COSMIC database that provides information on the availability and development of drugs targeting somatic mutations in cancer. COSMIC’s certified curation team integrates data from case studies, clinical trials, and regulatory bodies to represent a full picture of the current precision oncology pipeline (from drug development, through safety and clinical phases, to market and repurposing).

Actionability contains information on three core units: mutations, diseases and drugs. By capturing relations between these units, COSMIC’s team identifies existing and upcoming drugs that target specific genetic variants in different cancer types.

Releases of Actionability occur more frequently than COSMIC to better reflect the rapid pace of global precision oncology. Actionability is a cutting-edge, ‘living-tool’ that ensures you always have the latest, expert-certified data to inform therapeutic decision-making.

Actionability v14 release highlights​

The COSMIC Actionability database serves as a vital resource for identifying actionable mutations and associated therapies in cancer. The v14 release includes:

• 17 Newly Curated Genes: Expanding the database to 188 genes, further supporting research and clinical applications in precision oncology.
• Updated Clinical Trials: Existing trials have been thoroughly reviewed for new or updated results, reflecting the latest developments in drug approvals and efficacy.

→ View the full COSMIC Actionability v14 Release Notes here.

Want to learn more about COSMIC?​

Explore the industry-leading somatic mutation database and request free COSMIC sample data by clicking the link below. For more information on applications and case studies, check out our featured resources.

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Feature resources

In this white paper, learn how to prioritize and analyze PIK3CA driver mutations with the COSMIC Cancer Mutation Census

Download White Paper

In this case study, learn how a lab uses COSMIC to build a database to efficiently identify the HLA-I immunopeptidome

Download Case Study