The COSMIC

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The COSMIC database and web site
Catalogue Of Somatic Mutations In Cancer
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Known cancer genes in the human
genome www.sanger.ac.uk/genetics/CGP/Census
352 Cancer Genes
Germline mutation 66
Missense mutation 83
Nonsense mutation 60
Somatic mutation 317
Frameshift mutation 61
Amplification 7
Translocation 263
Large deletion 26
The literature contains small intragenic somatic
mutation data on over 200,000 tumours
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Example of the response to gefitinib in a patient
with refractory nonsmall-cell lung cancer and
a somatic mutation in EGFR.
Mutation data EGFR status
Other data sex age pathological type no. prior
regimens smoking status duration of
therapy overall survival ethnicity
Lynch et al, N. Engl. J. Med., 2004
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The ERK MAPKinase pathway
MEK inhibitor (CI-1040) IC50 values as a
function of BRAF and NRAS mutational status
Solit et al, Nature Jan 2006
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Updates of 163 DNA variation web site /
database quarter when last updated
Link was dead 50 Last updated before 2002
16 Date not obvious 27 Last updated after 2002
70
Number of sites
2002
2003
2004
2005
2006
Links taken from HGVS web site
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Why develop COSMIC?

• To preserve somatic mutation data
• To share somatic mutation data
• To standardise genotype and phenotype
  information
• To integrate published data with the output of
  the Cancer Genome Project

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Data types captured in COSMIC
Individual
Tumour
Gene
Mutations
Sequence change
Age, sex, Environmental variables
Classification
Reference sequence
Source Features
Links to other resources, Ensembl, OMIM
gtATGCCGATAGGAGCTAGGCTTAGCTTGACGGATGGCATGGCATTAGC
STTGGACTTTAGCSTGACAAGGACTTTAGCATAGGAT CAGGATTAGG
ATTGTAG
c.1799TgtA p.V600E
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Data flow in COSMIC
Scientific literature
Manual data curation
Web site
COSMIC
COSMIC
Data export
Cancer Genome Project Lab work
Lab DB (SNP)
Web site
External
Internal
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COSMIC web site
http//www.sanger.ac.uk/cosmic/
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Tissue summary
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Gene summary Rb1
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Gene histogram Rb1
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Gene / Tissue details Rb1
Tissue
Samples
Mutated
Links
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Individual sample details
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Data export and integration

• The data on the web site is available in multiple
  formats
• Export function from the web site for individual
  genes (HTML, csv, Excel)
• ftp.sanger.ac.uk csv and Excel for individual
  genes
• Oracle export of the whole database
• Integration with Ensembl
• COSMIC DAS track for Ensembl

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How to start and sustain a database/web site

• Scientific utility
• Attached to a project that is generating or
  using the data
• Contact with the users - cosmic_at_sanger.ac.uk
• - COSMIC-announce_at_sanger.ac.uk
• Publication
• Continued development
• COSMIC funding
• 2000 to 2011 Wellcome Trust 4 dedicated staff
  others infrastructure
• 2006 to 2009 GlaxoSmithKline 2 dedicated staff

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What is available in COSMIC?
Statistics for Feb 2006 release Experiments
228,669 Tumours 142,569 Mutant samples
25,176 Mutations 26,194 Papers curated
3,013 Genes 1,035
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Weekly Statistics for COSMIC sample content and
web site hits
Sample count
140,212
73,767
120,000
80,000
40,000
Web site hits
27,690
196,571
600,000
400,000
200,000
2004
2005
2006
Based on a 4 week average
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Cancer Cell Line Project
800 cancer cell lines 14 known cancer genes 978
mutations
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Future plans for COSMIC

• Curate more cancer genes, update existing genes
• Share data with other databases IARC TP53
  database
• Integrate other data from the CGP copy number
  data
• Further use of DAS and Ensembl
• Expand the number of queries and views on the
  web site
• Expand the export functions
• Display more unpublished mutation data from the
  Cancer Genome Project
• Display data from the NCI?