COSMIC, the Catalogue Of Somatic Mutations In Cancer, is the world's largest and most comprehensive resource for exploring the impact of somatic mutations in human cancer. When it was created in 2004 by researchers with the Cancer Genome Project in conjunction with the Sanger Institute, COSMIC was set up with a big ambition–to be the source of all cancer genomic knowledge.
Today, COSMIC contains nearly 24 million genomic variants across 6,800 precise forms of human cancer. It is the most expansive, expert-curated knowledge hub available for somatic NGS data analysis and interpretation. From molecular pathologists matching mutations to targeted therapies to bioinformaticians looking for patterns of DNA mutations in cancer cells, COSMIC is an excellent resource for identifying and understanding cancer mutations.
Now, as the demand for precision oncology increases, so does the need for a comprehensive cancer genomic knowledge base. Here are 5 reasons why you should be using COSMIC for biopharmaceutical research.
Precision is crucial in developing biopharmaceuticals. Unlike other somatic databases, COSMIC is meticulously and rigorously curated by a team of highly trained, PhD-level experts. This manual curation—the gold standard in genomic curation—ensures that every data point undergoes human scrutiny, giving scientists unparalleled confidence in the accuracy and consistency of the data they rely on. Through comprehensive literature searches, COSMIC’s experts have curated, standardized, and cataloged mutation data, phenotype information, and clinical details from over 1.5 million cancer samples and 29,000 peer-reviewed papers to date.
COSMIC provides an unmatched level of traceability for every data point, empowering scientists with transparency and fostering confidence in the presented evidence. With COSMIC, there is no 'black box'; each piece of information can be traced back to its source, providing users with complete visibility into its origins. This complete transparency is invaluable for biopharmaceutical scientists, especially when dealing with rare variants or variants of unknown significance. In these cases, users can independently assess each piece of data, exercising their judgment on whether to agree or disagree with COSMIC’s data for a particular variant.
In the pursuit of precision oncology, biopharmaceutical scientists must address a wide range of questions about somatic alterations as druggable targets. COSMIC stands as the largest repository of comprehensive genomic, phenotypic, and mutational characteristics of cancers. With COSMIC, you can obtain the most exhaustive information available on mutations associated with a specific cancer type, the frequency and tumor distribution of a specific alteration, driver oncogenic events, candidate therapeutic targets, and much more.
Furthermore, COSMIC’s Actionability functionality assists scientists in tracking and exploring drugs in various stages of development, monitoring the progress of clinical trials, and investigating drugs repurposed to target specific mutations.
And unlike other databases relying on volunteers, COSMIC is continually updated by its team of dedicated expert scientists, ensuring you have access to the accurate and up-to-date insights necessary to advance your translational research efforts.
In the dynamic field of biopharmaceuticals, adaptability is essential. COSMIC offers exceptional flexibility, enabling users to customize their data mining, visualization, and manipulation processes. COSMIC can be seamlessly integrated into your IT systems, allowing automatic updates or scheduled integration of newly released datasets to align with your individual workflow. COSMIC also allows you to customize filters according to your pipeline and fully integrate its data with proprietary databases to obtain a single comprehensive view. With COSMIC, you can easily align the data precisely with your unique research processes, enhancing your ability to extract actionable insights.
In biopharmaceutical research, credibility is earned through adoption. Over 50,000 molecular pathology labs, clinicians, bioinformaticians, and researchers worldwide trust and use COSMIC. It has also been cited in over 10,000 publications. Its extensive usage attests to its accuracy, consistency, and reliability. Recognized in the AMP/ASCO/CAP guidelines as a foundational evidence source for somatic variant assessments, COSMIC allows biopharmaceutical scientists to align their work with the highest standards in the field.
Trying COSMIC in your lab is easy. Simply visit the official COSMIC website, scroll to the bottom of the page, and "Request A Demo". One of our experts will contact you immediately about scheduling a free demo of COSMIC using your lab's data.
While the world showed its support for affected people during Breast Cancer Awareness Month, COSMIC's expert curators were working hard behind the scenes to get information on rare breast cancers ready for the upcoming release later that month.
Breast cancer is still a big global problem
Breast cancer is the most prevalent cancer type worldwide. At the end of 2020, there were 7.8 million women alive who’d been diagnosed with breast cancer in the previous five years. And despite leaps and bounds in detection and treatment, there were still 685,000 deaths from breast cancer in 2020 alone.
Nevertheless, the numbers are still fairly optimistic. Breast cancer mortality in high-income countries has dropped 40% between the 1980s and 2020 - and it’s continuing to drop by around 2-4% in these countries each year. Innovations in treatment and targeted drug therapies, such as trastuzumab to treat HER-2 positive cancers, are showing outstanding results. And let’s be clear, early detection and effective treatment is really the only option. Unlike many common cancers, even if all the risk factors for breast cancer development were controlled, this would only reduce the risk by 30%. A multi-pronged approach is needed- optimize care pathways, facilitate early diagnosis, and provide the right treatment at the right time.
And for treatment-resistant breast cancers? We need to understand what’s driving these cancers at a genetic level and identify targets for the next generation of drugs.
Cue COSMIC as the navigational tool that hosts the data to springboard scientific innovation. COSMIC’s latest release v95 (November 2021) has a special focus on rare female cancers, including the rarer breast cancer subtype with notorious poor outcomes, metaplastic breast cancer (MpBC).
The lowdown on metaplastic breast cancer
Metaplastic breast cancer is a rare and aggressive malignancy. Although the incidence is low (it only accounts for 0.2–5% of all breast cancers), MpBC accounts for a significant proportion of breast-cancer deaths.
MpBCs are usually (but not always) triple-negative - meaning they lack expression of estrogen receptor (ER), progesterone receptor (PR), and HER2. So, some of the revolutions in current treatments are ineffective. Like other triple-negative breast cancers, they’re more likely to present with distant metastasis, but they generally have a worse prognosis than their grade-matched counterparts.
Compared to other cancers, relatively little is known about MpBC, but more studies are happening all the time. Speaking of, time to look at some of the new datasets being incorporated into V95 of COSMIC.
Classification: Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications
When cancer is rare, it can be harder to create clear definitions, classifications, and guidance. This is especially true of MpBC, a cancer literally named for its heterogeneity in cell types. Metaplasia derives from Ancient Greek and means ‘change in form’. In this context, it’s the transformation of one differentiated cell type to another differentiated cell type. The World Health Organisation (WHO) guidelines currently rely on the structure, shape, and organization of the cells to create sub-categories - without any information on molecular causes or clinical guidance.
Caption: Table showing the various WHO classifications of metaplastic breast cancer [1]
But Lakhani et al. decided to look under the hood. Using strength in numbers, they formed the Asia-Pacific MpBC consortium to collect and study 347 MpBCs in depth.
What did the increased numbers provide? Let’s start with genetics. Exome sequencing was performed on 30 of the MpBC cases and found TP53, PTEN, and PIK3CA mutations co-occurring. This countered a long-held concept that TP53/PTEN and PI3CA/PTEN mutations were mutually exclusive.
Moving on to prognosis - the top question that patients have when diagnosed: ‘How bad is it’?’ This study shed a little light. The significant indicators of poor prognosis were large tumor size, loss of cytokeratin expression, EGFR overexpression, and the presence of more than three distinct morphological entities. On the flip side, favorable indicators included fewer morphological components and EGFR negativity.
With these findings, Lakhani et al. suggest minor changes to the WHO classification. The paper ends with the comment that, ‘thousands of samples would need to be reviewed centrally in order to tease out the subtleties required to make any bolder changes to the guidelines’. As more similar data is incorporated into COSMIC datasets, it will enable this scale of analysis.
New targets: Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers
Having discussed the WHO guidelines more broadly, time to zone in on one of the even rarer subtypes of MbBC, WHO_5: Spindle Cell Carcinoma. This subtype displays the previously mentioned triple-negative characteristic, as well as having an association with resistance to conventional chemotherapy.
Evidently, new tactics are needed. Precision oncology and immuno-oncology could provide some strategies for targeted therapies, but first we need to know if the right mutations and immune markers are present. Gatalica et al. studied this with some promising results.
They used 23 MpBC spindle cell carcinomas and thoroughly analyzed them using immunohistochemistry and DNA/RNA sequencing. And some familiar faces emerge here - PIK3CA, TP53, HRAS, NF1, and PTEN pathogenic gene mutations were identified in the majority (21) of cases. As highlighted by the authors, PIK3CA mutations are particularly relevant because they’ve been classified as strong predictors of response to PIK3CA inhibitors, and several drugs have either been recently approved, or are in the pipeline, for targeting the PI3K pathway, including Piqray (alpelisib).
Finally, onto the immuno-oncology markers. PD1 is a molecular ‘gun’ found on the surface of immune cells - when they spot a threat they attach and fire. Unless the cell in question puts out a defence - PD-L1 - which puts the safety on and prevents firing. Tumors can use PD-L1 as a means of escaping destruction by the immune system, so new drugs have been developed to block PDL1 and PD1 from binding. But there’s an added layer of complexity, if another molecule - PTEN - is present, then it’s indicated that drugs designed to target PD-L1/PD1 will be less effective.
PDL1 and PD1 molecules interacting on surface of cells. PD1 is purple and PDL-1 is yellow.
Back to the research. The study found evidence of PD-L1 expression, but only above the threshold for treatments in two cases. And two cases also had concurrent PTEN expression. So, for biomarkers, there’s promise that targeted therapies could work in some cases, but a thorough analysis would need to be done on a case by case basis.
Power in numbers
It’s promising to see this volume of new studies and big data being gathered for the rarer cancers. And it’s evident that the route forward is in numbers, collaborations, and collating evidence from multiple sources. Seeing the mounting evidence for PIK3CA expression involvement in MpBC is just one example of this. But without a centralized database, curated from thousands of papers that have been read and analyzed by trusted experts (with a passion for their work) it would be easy to miss key cases.
Reach out to the QIAGEN team to get access to this exciting data. Test it out for yourself – the first 100 lines of COSMIC are made available for free download.
[1] McCart Reed AE, Kalaw E, Nones K, Bettington M, Lim M, Bennett J, Johnstone K, Kutasovic JR, Saunus JM, Kazakoff S, Xu Q, Wood S, Holmes O, Leonard C, Reid LE, Black D, Niland C, Ferguson K, Gresshoff I, Raghavendra A, Harvey K, Cooper C, Liu C, Kalinowski L, Reid AS, Davidson M, Pearson JV, Pathmanathan N, Tse G, Papadimos D, Pathmanathan R, Harris G, Yamaguchi R, Tan PH, Fox SB, O'Toole SA, Simpson PT, Waddell N, Lakhani SR. Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications. J Pathol. 2019 Feb;247(2):214-227. doi: 10.1002/path.5184. Epub 2018 Dec 20. PMID: 30350370.
This year ESHG is celebrating it's 50th anniversary in beautiful Copenhagen! Come and meet us at booths 540 and 542 and find out how our solutions are helping to unlock the complexities of liquid biopsy, clinical oncology, hereditary disease, microbial genomics and more.
We're also hosting a lunchtime Corporate Satellite Meeting on Sunday, May 28 where lunch boxes are provided. Here's the schedule:
Using seamlessly integrated preanalytical, next-generation sequencing and bioinformatics solutions, and leveraging expertise in translational and clinical research to refine our understanding of human genetics and diseases
Time: 11.15 a.m. – 12.50 p.m.
Room: Berlin
Chair: Anja Wild and Phoebe Loh, QIAGEN, Hilden
11.15 a.m. – 11.20 a.m.
Welcome
11.20 a.m. – 11.50 a.m.
Molecular analysis of thyroid nodules – detection of gene mutations and fusion genes by DNA/RNA sequencing
Dr. Egbert Schulze, Molecular Genetics Laboratory, Heidelberg, Germany
11.50 a.m. – 12.15 p.m.
Circulating Cell Free DNA Pre-Analytics: Importance of ccfDNA Stabilization and Extraction for Liquid Biopsy Applications
Dr. Dominic O’Neil, QIAGEN, Hilden, Germany
12.15 p.m. – 12.45 p.m.
Leveraging Unique Molecular Indices to improve low-frequency variant estimation and calling in QIASeq v3 panels
Bjarni Vilhjalmsson, QIAGEN, Aarhus, Denmark
12.45 p.m. – 12.50 p.m.
Closing
As usual, we've prepared some poster presentations covering the latest enhancements to various application areas:
Electronic-poster number: E-P16.13
Presenter: Stuart Tugendreich, Principal Scientist, QIAGEN Bioinformatics
Title: Integrative approach to biomarker discovery by performing comparative analysis of two cancers Hepatocellular carcinoma and Endometrioid endometrial carcinoma using genetics and transcriptomics from RNA sequencing data.
Poster number: P14.049A
When: 10.15 a.m. - 11.15 a.m., Sunday, May 28
Presenter: Rupert Yip, Director of Global Product Management, Genetic Disease, QIAGEN Bioinformatics
Title: Prioritizing causal variants for rare, inherited syndromes, using patient phenotypes
We look forward to seeing as many of you there as possible.
Vi ses!
