The main COSMIC home page detailing current content statistics and top-level search options. The statistics are regenerated every release; in this case, the numbers relate to the October 2007 release. For color version of this figure see http://www.currentprotocols.com.

(A) The Gene overview page for KRAS, providing summary statistics of the mutation data, links to the data source overview pages (paper or study) and a series of links external to COSMIC. (B) For a gene with fusion data (e.g., TMPRSS2), an extra element is inserted after the graphical mutation summary, detailing its fusion partners and mutation statistics. For color version of this figure see http://www.currentprotocols.com.

Graphical representation of the mutation spectrum across the KRAS gene on the amino acid scale (A) and on the nucleotide scale (B). Note the novel introduction of complex mutations. Frequently two or three of these equal nucleotide substitutions, these often result in missense mutations at the peptide level, not separable in the amino acid view (A). The small popup menu (shown in B; available for all mutation types) offers zooming options and details links. For color version of this figure see http://www.currentprotocols.com.

(A) Details table from the histogram page, detailing the per-tissue and total sample counts and mutation rates. Only a small portion is shown; 13 tissue types are above “haematopoietic and lymphoid tissue” and 18 below “pancreas.” Clicking on the More Details column shows a small popup menu, linking to tabular details of the samples examined for the tissue type chosen. (B) Excerpt from the Mutations table on the histogram page viewed at the amino acid level, detailing (in this sample of a large table up to codon 13 of KRAS) each sequence variant observed on the gene, together with the number of times observed (in parentheses) and a link to its own summary page. Subsequently this table may display details of other mutation types. (C) Excerpt from the Mutations table of the histogram page, detailing at the nucleotide level all the sequence variants observed up to codon 13 (nucleotide 39) of KRAS. A count of each mutation is shown, together with a link to that mutation's summary page. For color version of this figure see http://www.currentprotocols.com.

The histogram graphic showing the cDNA view of KRAS when zoomed in to the mutation peak between 30 and 40 bp (of the CDS). For color version of this figure see http://www.currentprotocols.com.

The five most mutated genes in the specialized phenotype, ductal carcinoma of the pancreatic ampulla of Vater (Pancreas: Ampulla of Vater; Carcinoma: Ductal Carcinoma). The small popup menu summarizes the tabulated data for the selected gene, and a link to the histogram page. For color version of this figure see http://www.currentprotocols.com.

Starting from the Tissue Overview in Figure 10.14.6, the histogram and tables reflect specialized phenotypes, showing only the data from samples with this specific cancer type. For color version of this figure see http://www.currentprotocols.com.

The Mutation Summary page for the highly oncogenic c.35G>T KRAS mutation. All details of this mutation are presented here, including the Associated Samples list, which is a potentially very long list of samples in which this mutation has been found. Sample names and tissues are linked. For color version of this figure see http://www.currentprotocols.com.

COSMIC data viewed in the Ensembl genome browser, starting from the Mutation Summary in Figure 10.11.8. By default initially zoomed into the coordinates immediately around the mutation specified (KRAS c.35G>T), zooming out gives a view of the genomic context of the COSMIC gene and its mutation spectrum (crosses denote substitutions, filled triangles denote insertions and deletions). Closely positioned mutations are arranged vertically, so if there are many (as in KRAS), the page can become very long. Hashed grey horizontal bars have been used in the figure to indicate where data have been cut. For color version of this figure see http://www.currentprotocols.com.

Selected information boxes from the Sample Overview page, detailing a choice from the c.35G>T Mutation Summary page. This page can be very long, as it brings together all the information about the sample, which can be extensive. This figure only includes data of importance. Further details can include genotypically synonymous samples, external data sources with further information (LOH analysis, extensive genotyping), and further isolated data points extracted from the paper about the sample (e.g., stage, grade, ethnicity, karyotype). CGP samples often include a link to the CGP study, together with microsatellite instability and genotyping data. In this page, the list of mutations and nonmutant genes can be somewhat lengthy. For color version of this figure see http://www.currentprotocols.com.

(A) The information box displayed under the histogram when COSMIC has information on fusion events involving the selected gene (in this example, TMPRSS2). (B) The Fusion Summary page for the TMPRSS2/ETV1 gene pair. Inferred breakpoints are displayed in the table, and observed mRNAs are displayed graphically. Similar to the Mutation Summary page, there is a tabulated breakdown of mutation frequencies by primary tissue type. Finally, the publications used to generate the data are summarized. Clicking on a mutation ID or a graphically rendered transcript provides further information on that individual fusion mutation. For color version of this figure see http://www.currentprotocols.com.

The main COSMIC workflow. After initial selection of a gene or phenotype to examine, the detail pages link together in a web, allowing navigation through sample, gene, and mutation details, together with redefinition, specialization, or generalization of the initial selection. For color version of this figure see http://www.currentprotocols.com.

The COSMIC Web site overviews the data from three distinct subprojects. The gold pages describe the data derived from curation of the scientific literature, the red pages display results from the CGP resequencing project, and the green pages detail results of the cancer cell line project. The gold page is simply descriptive, while the green and red pages front Web sites that allow full independent navigation of the subproject's data. For color version of this figure see http://www.currentprotocols.com.

COSMIC's histogram can give an immediate indication of a gene's oncogenic mutability. (A) Gain-of-function. The KRAS histogram shows only a single spike of a missense mutations at residue 12, known to be the protein's key mutant position, regulating its transcriptional activation capacity via the MAP/ERK pathway. Mutating p.G12 causes a gain-of-function overactivation of downstream growth promotion signals, resulting in tumorigenesis. (B) Loss-of-function. The PTEN histogram, conversely, shows a wide mutation spectrum, spread across the entire gene's length and including all mutation types. This clear loss-of-function mutation pattern is indicative of a tumor suppressor gene, whereby tumorigenesis occurs after the gene's growth-inhibiting effect is destroyed. For color version of this figure see http://www.currentprotocols.com.

Using COSMIC's histogram to view the tissue-specific mutation spectra in the KRAS gene for (A) lung and (B) pancreas. For color version of this figure see http://www.currentprotocols.com.

The same data selection (a mutation summary of the ERBB2 gene, with domain structures removed) shows significantly different data when viewed between COSMIC's three color-coded Web sites: (A) the main COSMIC site (blue), (B) the CGP resequencing site (red), and (C) the Cancer Cell Line Project (green). For color version of this figure see http://www.currentprotocols.com.