Two expert-curated databases exclusively licensed through QIAGEN link sequence-level somatic mutation data to detailed molecular information about functional and clinical impacts, as well as implications for druggability and relevant clinical trials. The two databases, the Catalogue Of Somatic Mutations In Cancer (COSMIC) and the Human Somatic Mutation Database (HSMD), enable biopharmaceutical researchers to avoid pitfalls in early cancer drug discovery and development, confidently qualify candidate drug targets, and accelerate indication expansion and repurposing of existing cancer therapies.

In this blog, learn more about the high-level applications of using COSMIC and HSMD in cancer drug discovery and development pipelines.

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The Catalogue of Somatic Mutations in Cancer (COSMIC)

The Catalogue Of Somatic Mutations In Cancer (COSMIC) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. Developed and maintained by Wellcome Sanger Institute, the latest release, COSMIC v99 (December 2023), includes over 6 million coding mutations across 1.5 million tumor samples, curated from over 29,000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations.

COSMIC integrates somatic data from multiple sources published around the world and allows researchers to access and scrutinize information about somatic mutations and their impact in cancer. Over the past two decades, COSMIC, through predominantly manual curation workflows, has been diligently collecting, cleaning, and organizing genomic data and associated metadata from cancer studies published in scientific literature and various bioinformatics sources. This data is then translated into a standardized format, integrated, and made available to the research community through well-structured datasets and user-friendly data exploration websites and tools.

The Human Somatic Mutation Database (HSMD)

The Human Somatic Mutation Database (HSMD) is a relatively new somatic mutation database from QIAGEN (released in 2019) that combines over two decades of expert curation and data from scientific literature, on- and off-label therapies and clinical trials, and real-world clinical oncology cases. In the latest release, HSMD 3.0 (November 2023), the database contains manually curated, detailed molecular information on over 1.8 million somatic variants, with more than 430,000 observed in real clinical cases, as well as data from over 545,000 real-world clinical oncology cases.

Unique to HSMD is the availability of data from clinically observed variants. When a variant has been “clinically observed,” it means QIAGEN’s professional clinical interpretation service (previously N-of-One) has encountered this alteration in a real-world clinical case. For these variants, QIAGEN assesses the clinical and biological relevance and calculates the gene and variant prevalence across observed tumor types.

Easy to search with new content added weekly, HSMD enables researchers to explore key genes or mutations with driving properties or clinical relevance and search for associated treatment options, off-label therapies, resistance markers, and regional and/or disease-specific clinical trials.

Applications of COSMIC and HSMD in cancer drug discovery and development

While similar, COSMIC and HSMD differ in their applications for cancer drug discovery and development. As a result, biopharmaceutical researchers can use both databases to support different workflow stages.

How COSMIC supports exploratory research in cancer drug discovery

COSMIC is a valuable resource for cancer researchers and drug discovery efforts. Here are several ways in which the COSMIC database can be used to support exploratory research in cancer drug discovery:

• Identification of mutations in target genes - COSMIC provides a comprehensive catalog of somatic mutations observed in various cancer types. Researchers can use COSMIC to identify mutations occurring in the gene associated with the drug target. Evaluating the prevalence and distribution of mutations can help assess the potential impact on the function of the target.

• Frequency of mutations across cancer types - Analyzing COSMIC data allows researchers to assess the frequency of mutations in the target gene across different cancer types. Higher mutation frequencies in specific cancer types may indicate the relevance of the target in those cancers, supporting its potential as a drug target.

• Correlation with clinical data - COSMIC integrates clinical data, including patient outcomes. Researchers can correlate mutations in the target gene with clinical parameters such as patient survival, response to treatment, or disease progression. Positive correlations may suggest the potential significance of the target in predicting clinical outcomes.

• Functional impact of mutations - COSMIC provides information on the functional impact of specific mutations. Understanding whether mutations in the target gene are driver mutations (contributing to cancer development) or passenger mutations (incidental changes) is crucial. Driver mutations are more likely to validate the target as a potential therapeutic intervention.

• Validation across datasets - Researchers can cross-validate findings from COSMIC by comparing them with data from other sources, such as The Cancer Genome Atlas (TCGA) or other cancer genomics databases. Consistency across multiple datasets strengthens the validity of the target.

• Exploration of drug response data - COSMIC includes data on drug response, allowing researchers to explore how cancer cell lines with specific mutations in the target gene respond to different drugs. Assessing drug response data helps predict potential therapeutic strategies and identifies drugs that may be effective against cancers with specific mutations in the target.

• Integration with pathway analysis - COSMIC provides information on pathways associated with mutated genes. Researchers can integrate this data with pathway analysis tools to understand the broader biological context of the target. Pathway analysis helps identify potential interactions and dependencies that can further validate the significance of the target.

How HSMD supports cancer drug clinical development and post-market research

HSMD is a valuable resource for biopharmaceutical researchers, facilitating the confident evaluation of cancer-related genetic variations by granting access to real-world data. Here are several ways in which HSMD supports cancer drug clinical development and post-market research.

• Identify clinical function of somatic mutations - HSMD enables researchers to easily search and explore mutational characteristics across genes, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant.

• Conduct research use only (RUO) studies - Researchers can leverage HSMD to deepen their understanding of disease mechanisms at the molecular level. RUO studies can explore how specific genetic alterations contribute to disease initiation, progression, and resistance, providing insights into potential therapeutic interventions.

• Clinical trial optimization – HSMD contribute significantly to clinical trial optimization by facilitating patient recruitment, informing trial design, and providing valuable insights throughout the trial lifecycle.
  • Patient stratification – The real-world, de-identified patient data in HSMD enables the identification of eligible patients based on specific criteria for clinical trials. Improved patient identification streamlines recruitment efforts, accelerates trial enrollment, and reduces the time and costs associated with the initiation phase.

• • Clinical trial feasibility assessment – With clinical trial data that can be segmented by geographic location, HSMD can used to assess the feasibility of conducting a clinical trial at specific sites or within particular patient populations. Understanding patient demographics, disease prevalence, and historical treatment patterns aids in identifying suitable trial locations and estimating recruitment potential.

• • Regulatory submission and approval – HSMD data can complement traditional clinical trial data in regulatory submissions, providing additional evidence of a treatment's effectiveness and safety. Regulatory agencies increasingly recognize the value of real-world evidence in supporting decision-making during drug approval processes.

• • Companion diagnostic design – Users can search HSMD by disease and receive a ranked list of associated genes to help design custom assays that enable better prediction of response and resistance to specific therapies.

• Drug repurposing - HSMD enables the analysis of the frequency and distribution of somatic mutations across various cancer types. The database also provides a catalog of drugs employed in the treatment of patients with specific mutations, along with available response data. Using this information, researchers can explore potential new indications for existing cancer drugs.

Transform targets into precision cancer therapies

COSMIC and HSMD are two expert-curated databases licensed exclusively through QIAGEN that enable biopharmaceutical companies to improve the drug discovery process, develop more effective clinical trials, and enhance the treatment of rare cancers. To learn more about how your research team can use COSMIC and HSMD, visit our product webpage or click the button below for a free trial and personal consultation with our biopharmaceutical research experts.

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The Cancer Gene Census (CGC) catalogues genes with mutations causally implicated in cancer and explains how dysfunction of these genes drives cancer.

New genes and annotations

With COSMIC v99, new high-quality genes have been added to the CGC ─ three to Tier 1 and three to Tier 2. The genes are HGF, RAD50, RRAS2, GSK3B, MUC6 and RAP1B.

More, cancer hallmark annotations have been added to each of the 8 existing CGC Tier 1 genes (SRC, SRSF2, STAT3, STAT5B, STK11, SUFU, TBX3, TNFRSF14). Cancer hallmark annotations summarize the effect of Tier 1 genes on the phenotypic traits shared by cancers.

Tier changes

The CGC has been compiled over 19 years and is periodically reviewed. This ensures that gene assignment to the Census reflects the latest evidence indicative of the strength of a causal association between a gene and one, or more, cancer types, and consistency in the application of the COSMIC inclusion criteria for CGC Tier 1 and Tier 2 assignment. Based on this, and following a recent review, TSHR has been re-assigned from Tier 1 of the Census to Tier 2, and its previous designation as an oncogene rescinded.

What else is new in COSMIC v99?

• 32 new systematic screen papers
• 5 manually curated cancer genes ─ IKZF3, ARHGAP35, BAX, ASPM, GSK3B
• 438,063 new genomic variants, +1 million new coding mutations, 274,853 new non-coding mutations, 6,810 new samples and 1,303 new whole genomes
• Updated Cancer Mutation Census (CMC) data that aligns with the latest COSMIC

→ Want more details? Read the full COSMIC v99 release notes here.

Gentle reminder: make the switch to COSMIC's new, improved download files

v99 is the second release available through COSMIC's new, improved download files. These new files contain the same gold standard COSMIC data found in its current files, but presented in a more accessible and interoperable manner.

What’s new?

1. A new, clear, consistent naming convention which all files follow. 
2. Each project and product have been packaged with ReadMe files individually.
3. Refined columns within the files.
4. Improved IDs which are consistent across both download files and webpages.

Transitioning to COSMIC's new files

The COSMIC team wants to lead by example in encouraging data to be FAIR (Findable, Accessible, Interoperable and Reusable) compliant, and as part of this goal, they will be phasing out their current files for COSMIC v100 in May 2024. This means that the current download files will be retired and only the new style files will be available to download. 

→ Learn more about COSMIC's new files and transition support here.

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Nearly two dozen new fully curated somatic genes and 387 clinical trials included in COSMIC Actionability v8 release

We are pleased to announce the availability of a new release for COSMIC, the Catalogue of Somatic Mutations in Cancer. COSMIC Actionability v8 adds new actionability data to the world’s largest, expert-curated somatic mutation database. The release includes 22 new fully curated somatic genes, 387 new clinical trials, and 166 new oncology drugs.

In this article, we provide a summary of the COSMIC Actionability v8 release highlights.

What is COSMIC?

COSMIC, the Catalogue of Somatic Mutations in Cancer, 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 23 million somatic mutations associated with human cancers.

What is COSMIC Actionability?

COSMIC Actionability is a standalone product within the COSMIC database that focuses on providing 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.  COSMIC Actionability is a cutting-edge, ‘living-tool’ that provides the most up-to-date data for precision oncology applications.

What’s new in COSMIC v8 Actionability?

• 22 additional fully curated genes: ATR, BCL2, CD33, CDKN2A, CHEK2, ERBB4, FBXW7, GNAS, MAP2K2, MTOR, MYD88, NOTCH1, NTRK1, NTRK2, NTRK3, PALB2, PIK3CB, PTPN11, RAF1, SYK, TERT, VHL.
• 387 new clinical trials:  COSMIC Actionability now contains 3,977 trials with results and 5,431 trials with no results. As a result, there is now a total of 9,408 clinical trials.
• 166 new drugs: COSMIC Actionability now contains 1,686 drugs.
• 70 new somatic variants: With the new release, COSMIC Actionability now contains 834 total somatic variants.

→ View the full Actionability v8 release notes here.

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 by downloading sample data here.