Variant Interpretation for Cancer (VIC): a computational tool for Nature 417: 949954 [6] These four genes are known to be somatically mutated in cancer. After querying the database, the results are displayed as a figure (Figure 1) and as a series of tables (Table 2) for each gene that was selected. All the information is referenced with links to the literature source via PubMed provided on the page. Forbes SA, Tang G, Bindal N, Bamford S, Dawson E, Cole C, Kok CY, Jia M, Ewing R, Menzies A, Teague JW, Stratton MR, Futreal PA. Nucleic Acids Res. Accessibility Clin Gastroenterol Hepatol. +44 (0)1223 834244, Wellcome Sanger Institute, Genome Research Limited (reg no. PubMed Central Use: This dataset is publicly available for anyone to use under the . PMC This data provides a new way to explore and understand the mutations that drive cancer. NGS-Based Tumor-Informed Analysis of Circulating Tumor DNA. COSMIC Website: cancer.sanger.ac.uk/cosmic. cBioPortal for Cancer Genomics Hum Mutat 19: 607614, Reddy EP, Reynolds RK, Santos E, Barbacid M (1982) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. The listings in each category have links to the relevant overview pages in the COSMIC website. Cite this article. Figure S3. Forbes S.A., Beare D., Boutselakis H., Bamford S., Bindal N., Tate J., Cole C.G., Ward S., Dawson E., Ponting L. et al. Direct accessibility via web, user-friendly environment and computational performance are key factors of our application. The minimum information required is the chromosome and genomic position according to the human reference genome (UCSC GRCh38/hg38, GRCh37/hg19 and 1000genomes hs37d5 builds are supported), as well as the reference and alternative alleles for every mutation. As this is one of the supported input formats in MuSiCa, the application permitted to directly analyze this publicly available repository. It starts with the uploading of the files containing the somatic SNVs of the samples to analyze. Once this initial curation is released, the gene is updated as significant new information is published. Welcome to the COSMIC Help Pages. For somatic mutations in cancer, there are many locus-specific web resources, such as those for p53 (Olivier et al, 2002; Broud and Soussi, 2003), that cover a single gene in depth. The tissue site and histology data is taken from the curated papers and entered into COSMIC (this forms the paper definition). The repertoire of mutations across TP53 are represented on a protein structure in three dimensions (PDB id: 4HJE). Having displayed the results from a query, the data can be formatted in simple text, Excel or HTML that can be downloaded from the COSMIC site. In the tumours that have been analysed, there are a total of 10647 mutations, 736 in BRAF, 477 in HRAS, 8302 in KRAS2 and 1132 in NRAS. This information is maintained in a separate, but parallel system alongside COSMIC and regularly updated to highlight the most valuable information across the cell line panel. They corresponded to the TCGA-COAD project. The .gov means its official. VarStack is a web tool which is a base to retrieve somatic variant data relating to cancer from existing databases. Nucleic Acids Res. Over the past 25 years, approximately 300 genes have been shown to be somatically mutated in cancer (Futreal et al, 2004). In parallel, cancer genomes are curated via a more bioinformatic approach. Output elements are displayed in six different tabs. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website have been developed to store somatic mutation data in a single location and display the data and other information related to human cancer. The figure shows the CDKN2A gene, which is a tumor suppressor that leads to cancer when it is inactivated. There is a continuing effort to enter additional somatic mutation data in to COSMIC. COSMIC (Catalogue of Somatic Mutations in Cancer) is a data resource that is designed to store and display somatic mutation information and related details and contains information relating to human cancers. 2010 Jan;38(Database issue):D652-7. Combinatorial patterns of somatic gene mutations in cancer. J Immunother Cancer. Names of primary tumours are often more abstract, sometimes numeric ('1','2'), and often completely absent, in which case they are assigned a 6 or 7-digit name reflecting their database ID. Both assessments were highly significant ( P = 2e-62, P = 2e-50, hypergeometric test) suggesting that the hotspot database is highly enriched in cancer genes and cancer genes under positive selection. -, Futreal P.A., Andrew Futreal P., Coin L., Marshall M., Down T., Hubbard T., Wooster R., Rahman N., Stratton M.R.. A census of human cancer genes. A number of tumours can be examined from a single cancer patient, and a number of samples can be examined from each of these tumours. The initial output from COSMIC is a graphical view of the mutations distributed along the linear amino-acid sequence of the gene. The depth of the stratification relates to the depth of the original query. Shiraishi Y, Tremmel G, Miyano S, Stephens M. A simple model-based approach to inferring and visualizing Cancer mutation signatures. Available from: https://cran.r-project.org/package=shiny. The COSMIC website will be developed further to make use of the underlying data. For MAF format, only one multi-sample file is allowed. A total of 513 tissue definitions have been noted in the papers in COSMIC and have been translated to 372 COSMIC tissue definitions. COSMIC is an ongoing project that will continue to curate somatic mutation data and release it through the website. doi: 10.1093/nar/gkp995. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/, Bamford, S., Dawson, E., Forbes, S. et al. The https:// ensures that you are connecting to the Clinically actionable cancer somatic variants (CACSV): a tumor Forbes SA, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J, Cole CG, Ward S, Dawson E, Ponting L, Stefancsik R, Harsha B, Kok CY, Jia M, Jubb H, Sondka Z, Thompson S, De T, Campbell PJ. doi: 10.1371/journal.pone.0090761. 1985;182:4565. Analysis workflow of MuSiCa. Advances in genome screening technologies have been the driving force behind the large increase in cancer mutation data, as well as the availability of copy number, gene expression and methylation . Signatures of mutational processes in human cancer. et al. In this regard, we have developed a web application to overcome these challenges. Mutational signatures have been proved as a valuable pattern in somatic genomics, mainly regarding cancer, with a potential application as a biomarker in clinical practice. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. 2023 Jun;11(6):e006284. Comparison of Open-access Databases for Clinical Variant Interpretation The COSMIC group make this information available in many ways to suit a variety of scientific and informatic users. Goncearenco A, Rager SL, Li M, Sang Q-X, Rogozin IB, Panchenko AR. These results are dispersed across the scientific literature and with the availability of the human genome sequence will continue to accrue. 2015;31:36735. Nature 300: 149152, Stajich JE, Block D, Boulez K, Brenner SE, Chervitz SA, Dagdigian C, Fuellen G, Gilbert JG, Korf I, Lapp H, Lehvaslaiho H, Matsalla C, Mungall CJ, Osborne BI, Pocock MR, Schattner P, Senger M, Stein LD, Stupka E, Wilkinson MD, Birney E (2002) The Bioperl toolkit: Perl modules for the life sciences. Tab-Separated Values (TSV), Excel and Mutation Annotation Format (MAF) are also allowed. These abnormalities include base substitutions, deletions, amplifications and rearrangements. If the gene has Pfam families associated with it, these are shown next, along with any Pfam annotations, such as the metal ion binding sites as here in TP53. A sample is a cell line or single piece of tumour examined through one or more genes for mutations. The application also permits clustering samples and signatures according to the contributions using a distance measure based on Pearson correlation (1 correlation value), as well as selecting which samples and cancer types are represented. In recent years, a new methodology has arisen on this field. Part of -. and JavaScript. MuSiCa also presents some extra features specially designed for cancer samples characterization. The website is focused on presenting complex phenotype-specific mutation data in a graphical manner. This method permits to find the optimal linear combination of the 30 signatures that minimize the residual sum of squares (RSS). 2008 Dec 9;10:e37. MutSpec: a galaxy toolbox for streamlined analyses of somatic mutation spectra in human and mouse cancer genomes. This methodology has the potential to reconstruct the mutational spectrum of any cancer sample with sufficient accuracy. Privacy By gene 30, 249, 718 and 303 papers report BRAF, HRAS, KRAS2 and NRAS mutations, respectively. Human Somatic Mutation Database | QIAGEN Digital Insights Steering and controlling evolution - from bioengineering to fighting pathogens. There are currently 1483 papers in COSMIC, 865 of these have been curated for mutations, while 618 either have no relevant data or incomplete data that could not accurately be extracted. [10][11] Secondly, data for inclusion in the database is collected from whole genome resequencing studies of cancer samples undertaken by the Cancer Genome Project. When zoomed in sufficiently, the amino acid sequence itself is shown beneath. The Wellcome Sanger Institute's COSMIC (Catalogue of Somatic Mutations in Cancer) database is the world's most extensive and comprehensive digital repository of somatic mutations in cancer. Selection of high-impact genes from this list for curation drives COSMIC. 2004; 91:355358. Mutational Signatures in Cancer (MuSiCa) allows an easy and quick analysis of mutational signatures in cancer samples, based on a user-friendly web environment adapted to the whole research community. All source code has been made publicly available on Github at: https://github.com/marcos-diazg/musica. -, Collins F.S., Barker A.D.. Mapping the cancer genome. -, Broud C, Soussi T (2003) The UMD-p53 database: new mutations and analysis tools. The work was carried out (in part) at the Esther Koplowitz Centre, Barcelona. MDG, MVC, SFE and SCB conceived the idea. CAS To populate this resource, data has currently been extracted from reports in the scientific literature for somatic mutations in four genes, BRAF, HRAS, KRAS2 and NRAS. In reference to bioinformatic packages, some different options were available as previously mentioned. Epub 2008 Apr 23. As we enhance the number of genes under curation, and the scope of data we aim to capture, an expansion of this team will ensure that COSMIC continues to succeed in supporting a wide range of oncology research and product development. a tab for each category. 2015;11:e1005657. Approximately one in three individuals in Europe and North America develops one of the approximately 200 different classes of cancer and it is the cause of death of one in five (Higginson, 1992). Based on the defining work by D. Hanahan and R. A. Weinberg published in Cell, COSMIC, in collaboration with Open Targets has integrated these key hallmarks into the Cancer Gene Census. According to the current information of the Catalogue of Somatic Mutations in Cancer (COSMIC) database , thirty mutational signatures have already been identified across 40 different types of human cancer . The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website have been developed to store somatic mutation data in a single location and display the data and other information. MAF format is commonly used for packing multi-sample data from the Genomics Data Commons projects. BMC Bioinformatics Noonan, Costello and cardio-facio-cutaneous syndromes: dysregulation of the Ras-MAPK pathway. It integrates different publicly available R packages in order to generate a convenient interface and computational efficiency to fluently handle somatic mutation data. About COSMIC Mutagenic specificity of ultraviolet light. To obtain Therefore, RSS is a measure of the efficiency of the original mutational profile reconstruction. Figure S2. COSMIC is the gold standard database for somatic mutation information. Pan-cancer Analysis of Advanced and Metastatic Tumors (BCGSC, Nature Cancer 2020) 570 samples. 2017;358:2348. errors identified in the data) are not fully curated but are added to a list of additional references containing somatic mutation information. Nordentoft I, Birkenkamp-Demtrder K, Dyrskjt L. Methods Mol Biol. Four hundred thirty-three samples of this neoplasia were analyzed. Bioinformatics. Identification of the genes that are mutated in cancer is a central aim of cancer research. 2742969) is a charity registered in England with number 1021457, 2023 Wellcome Sanger Institute | All rights reserved. Results of the analysis of colorectal cancer TCGA samples with MuSiCa are presented in Fig. Nat Rev Cancer. Cancer Gene Census Hallmark detail page. 2007; 296:5057. To incorporate the mutation data, we obtained the complete mutation data from the Catalogue Of Somatic Mutations In Cancer (COSMIC) database [15] by accessing downloads section (version v97 . Raf proteins and cancer: B-Raf is identified as a mutational target. Nucleic Acids Res 32: D468D470, Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Provided by the Springer Nature SharedIt content-sharing initiative. New York: McGraw Hill, Wheeler DL, Church DM, Edgar R, Federhen S, Helmberg W, Madden TL, Pontius JU, Schuler GD, Schriml LM, Sequeira E, Suzek TO, Tatusova TA, Wagner L (2004) Database resources of the National Center for Biotechnology Information: update. . COSMIC: the Catalogue Of Somatic Mutations In Cancer Introduction to COSMIC The extent to which each of these mechanisms contributes to cancer varies markedly between different genes, and probably also between different cancer types. The details of the papers that have been curated are maintained in the paper section and include title, journal, author lists and links to PubMed. Along with this, the home page provides information about the latest updates in COSMIC with current statistics and links to the additional CGP (Cancer Genome Project) resources. In this work we present Mutational Signatures in Cancer (MuSiCa), a new web tool based on MutationalPatterns and built using the Shiny framework in R language. By means of a simple interface suited to non-specialized researchers, it provides a comprehensive analysis of the somatic mutational status of the supplied cancer samples. Their identical ancestry is indicated how? This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication, Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer EL, Studholme DJ, Yeats C, Eddy SR (2004) The Pfam protein families database. The COSMIC database is the largest and likely the most comprehensive resource for exploring the clinical impacts of somatic mutations in various types of cancer. COSMIC is now under licence, with academic access available freely and commercial access available for a licence fee. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. 2018;46:D96470. Cambridge Monographs on Cancer Research. The search box on COSMIC's home page provides access to web pages where the data set can be examined with the help of various graphical and tabular views. COSMIC: Upon selection of a gene from the Census for full expert curation, all papers mentioning its mutation in human cancer are collected and exhaustively curated before it is released into a new version of COSMIC. By 2005 COSMIC contained 529 genes screened from 115,327 tumours, describing 20,981 mutations. Nucleic Acids Res 30: 387391 2016;17:170. However, they also showed the impact of age-associated signature 1. Terms and Conditions, Hum Mutat 21: 577581, Vogelstein B, Kinzler K (1998) The Genetic Basis of Human Cancer. An official website of the United States government. FOIA Comparison of Pathogenicity Prediction Tools on Somatic Variants Through the web pages, these data can be queried, displayed as figures or tables and exported in a number of formats. Rosenthal R, McGranahan N, Herrero J, Taylor BS, Swanton C. deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. Petkovic M, Yalin M, Heese O, Relgio A. BMC Med Genomics. However in the COSMIC scheme, each sample is unique and could be considered as a single experiment. Due to the complexity of the gene products, structures of only 87 genes have been solved experimentally with structural coverage between 90% and 100%. See this image and copyright information in PMC. Nature 303: 396400, Higginson J (1992) Human cancer: epidemiology and environmental causes. However, defects in key molecular pathways, especially those related with DNA repair, have been established as key factors in this neoplasm. This will include a DNA view of the mutations and methods to display insertions and deletions. J Mol Evol. 2013;500:41521. RSS is also shown, as well as cosine similarity between both profiles. Involvement in each of the relevant hallmarks of cancer is concisely characterized with the indication whether the protein in its wild-type form promotes or suppresses each hallmark. The scale bar incorporates a zoom function to generate a more detailed view of the protein to the point where individual amino acids are named (when there are fewer than 31 amino acids displayed). Google Scholar. The user has the option to select one or more tissues, then one or more histologies, and finally one or more genes. 2017;45:W51422. link on the COSMIC home page as is the Classification Scheme. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and The scale bar incorporates a zoom function to generate a more detailed view of the protein to the point where individual amino acids are named (when there are fewer than 31 amino acids displayed). It is mainly built on top of the MutationalPatterns package, so benefiting from its functionalities but also adding a graphical interface designed for non-specialized researchers. Cookies policy. Pan-cancer analysis of whole genomes (ICGC/TCGA, Nature 2020) 2922 samples. By using this website, you agree to our Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S, Sasaki N, et al. CB10 1SA. sharing sensitive information, make sure youre on a federal HHS Vulnerability Disclosure, Help Links from this table reload the figure to display a subset of the data and provide more details of the specific mutations. The table gives a summary of the mutations stratified by tissue and histology. Regarding mutational signature framework, MuSiCa uses the data available in COSMIC. 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. Regarding the quantification of COSMIC signatures, clustering discriminated at least three different subsets of colon cancer samples in this cohort. Standard pipelines (eg Ensembl VEP) annotate these genomic data in genic terms for COSMIC release. This site needs JavaScript to work properly. COSMIC is an online database of somatically acquired mutations found in human cancer. COSMIC - Database Commons The name of the sample is defined by the data source. Please enable it to take advantage of the complete set of features! The COSMIC (Catalogue of Somatic Mutations in Cancer) database and There are however limitations to this data as we can only collect data that is described in the original work. CAS 2018;10:33. The value of these various databases should not be underestimated; however, none of them offer a comprehensive view of all previously reported somatic mutations in cancer. A . Thus, it constitutes the imprint on the genome of specific mutagenic agents or genetic defects, each represented by a specific signature. Bookshelf Cancer Gene Census: This is a list of hundreds of genes with substantial published evidence in oncology. Cell Rep. 2013;3:24659. The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. At present, the database holds information on 66634 samples and reports a total of 10647 mutations. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. A principal component analysis (PCA) plot is also presented when more than three samples are uploaded. Article It includes a large repository regarding mutational signatures, but it is more focused on the analysis of publicly available datasets than samples directly provided by the users. Catalogue of Somatic Mutations in Cancer Cancer is a heterogeneous group of diseases, which is caused by the accumulation of mutations in genes that control cell activities, such as proliferation and apoptosis [].Mutations reported by the Cancer Genome Consortium (ICGC) [] and the Catalogue of Somatic Mutations in Cancer (COSMIC) [] show that most cancer cells possess 60 or more mutations []. To further ease the navigation of the system, we also have Youtube Help tutorial videos. Regarding developed software for mutational signature analysis, some other tools were already available. This forms the core of the COSMIC database. 2008 Aug;22(8):2605-22. doi: 10.1096/fj.08-108985. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Ardin M, Cahais V, Castells X, Bouaoun L, Byrnes G, Herceg Z, et al. Before BMC Bioinformatics 19, 224 (2018). Colorectal cancer is one of leading neoplasms worldwide considering mortality and morbidity. Alexandrov LB, Nik-Zainal S, Wedge DC, Campbell PJ, Stratton MR. Deciphering signatures of mutational processes operative in human cancer. Hallmarks of Cancer COSMIC, an acronym of Catalogue Of Somatic Mutations In Cancer, curates data from papers in the scientific literature and large scale experimental screens from the Cancer Genome Project at the Sanger Institute. In fact, regarding this last point, it permits analyzing a set of samples but cannot generate analysis reports on a single sample level. The Catalogue Of Somatic Mutations In Cancer (COSMIC) is a comprehensive database of somatic mutations. This value presents instead a direct measure of the correspondence between the two depicted profiles in a 01 range (identical profiles would have a value of 1). If there is no data for any of these definitions, COSMIC records an entry of NS, not specified. Pages showing data, such as the gene page, here shown for TP53, have been redesigned and restyled, with the page divided clearly into distinct sections. volume19, Articlenumber:224 (2018) Genome Biol. These results are dispersed across the scientific literature and with the availability of the human genome sequence will continue to accrue. Clipboard, Search History, and several other advanced features are temporarily unavailable. However, analysis of somatic mutational signatures remains currently inaccessible for a substantial proportion of the scientific community. Figure S1. These experiments can happen in a number of ways, but usually involve sequencing. The initial output from COSMIC is a graphical view of the mutations distributed along the linear amino-acid sequence of the gene. Several bioinformatic approaches have been developed to address mutational signature analysis using different platforms and programming languages. Utilising careful manual curation, 116 census genes have so far been . Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks. British Journal of Cancer and transmitted securely. 2016;538:2604. This process of signatures quantification is based on the least squares method. Samples may be derived from international studies as ICGC/TCGA or directly provided by the users. Nucleic Acids Res 32: D35D40. In addition, it also permits the quantification of COSMIC-reported signatures by finding their optimal linear combination. -, International Cancer Genome Consortium Hudson T.J., Anderson W., Artez A., Barker A.D., Bell C., Bernab R.R., Bhan M.K., Calvo F., Eerola I. et al. Google Scholar. The initial output from COSMIC is a graphical view of the mutations distributed, MeSH Article Most accessibly, it can be viewed and analysed in its custom website (https://cancer.sanger.ac.uk), where distributions across genes, genomes and diseases can be explored easily and in detail. DATABASE CONTENT For years, the COSMIC database has described somatic mutations in key cancer genes across many cancer samples, and, more recently, gene fusions and structural rearrangement annotations have been included. 2004; 4:177183. For example, by. The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. MDG and SFE are supported by contracts from FI 2017 (B00619, AGAUR, Generalitat de Catalunya) and CIBEREHD, respectively. doi: 10.1017/S1462399408000902. Nat. COSMIC, the Catalogue of Somatic Mutations in Cancer, is the world's largest expert-curated somatic mutation database. FASEB J. The group on the left, accounting for more than half of the samples, was mainly characterized by signature 1. This is particularly important in the case of hypermutated tumors, defined as those having a mutation rate above 12 per 106. (PDF) The COSMIC (Catalogue of Somatic Mutations in Cancer) database Introduction. Any type of agent or defect is responsible for a specific footprint in the form of a different burden and pattern of mutations. COSMIC: somatic cancer genetics at high-resolution. Reconstruction of mutational profile in MuSiCa web app. Tissue-specific mutation accumulation in human adult stem cells during life. For full details, see COSMIC in BigQuery hosted by ISB-CGC. Google Scholar, Chang W, Cheng J, Allaire JJ, Xie Y, McPherson J. A toggle in the filter panel in the gene page may be used to switch the view from amino acid to nucleic acid coordinate systems, and the switch is reflected in the exact data that is available in the histogram. Nucleic Acids Res. https://doi.org/10.1038/sj.bjc.6601894, DOI: https://doi.org/10.1038/sj.bjc.6601894. Nat Rev Cancer 4: 177183, Hall A, Marshall CJ, Spurr NK, Weiss RA (1983) Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Valle L. Recent discoveries in the genetics of familial colorectal Cancer and polyposis. A total of 96 possibilities are evaluated, allowing to detect processes responsible for the same substitutions but in different contexts. 8600 Rockville Pike MuTect2-derived data was selected in this example in accordance with GATK Best Practices [15]. Data is taken from selected genes, initially in the Cancer Gene Census, as well as literature search from PubMed. Since all cancers are caused by somatic mutations, this methodology has the potential to provide insight into their underlying biological processes and become a biomarker in clinical practice [3].