COSMIC is an online database of

somatic Somatic may refer to: * Somatic (biology), referring to the cells of the body in contrast to the germ line cells ** Somatic cell, a non-gametic cell in a multicellular organism * Somatic nervous system, the portion of the vertebrate nervous syst ...

ally acquired

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

found in human

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Somatic mutations are those that occur in non-

germline In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...

cells that are not inherited by children. COSMIC, an acronym of ''Catalogue Of Somatic Mutations In Cancer'', curates data from papers in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

and large scale experimental screens from the Cancer Genome Project at the

Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit organisation, non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is l ...

. The database is freely available to academic researchers and commercially licensed to others.

Creation and history

The COSMIC (Catalogue of Somatic Mutations in Cancer) database was designed to collect and display information on somatic mutations in cancer. It was launched in 2004, with data from just four

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

HRAS GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 (human), chromosome 11 at position 15.5, ...

, KRAS2, NRAS and BRAF. These four genes are known to be somatically mutated in cancer. Since its creation, the database has expanded rapidly. By 2005 COSMIC contained 529 genes screened from 115,327 tumours, describing 20,981 mutations. By August 2009 it contained information from 1.5 million experiments performed, encompassing 13,423 genes in almost 370,000 tumours and describing over 90,000 mutations. COSMIC version 48, released in July 2010, incorporates mutation data from

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

in collaboration with the

International Agency for Research on Cancer The International Agency for Research on Cancer (IARC; ) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and coordinate research into the causes of cancer. It also cance ...

. In addition, it provided updated gene co-ordinates for the most recent human

reference genome A reference genome (also known as a reference assembly) is a digital nucleic acid sequence database, assembled by scientists as a representative example of the genome, set of genes in one idealized individual organism of a species. As they are a ...

builds. This release includes data from over 2.76 million experiments on over half a million tumours. The number of mutations documented in this release totals 141,212. The website is focused on presenting complex phenotype-specific mutation data in a graphical manner. Data is taken from selected genes, initially in the Cancer Gene Census, as well as literature search from

PubMed PubMed is an openly accessible, free database which includes primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institute ...

Process

Data can be accessed via selection of a gene or cancer tissue type (

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

), either using ''browse by'' features or the ''search'' box. Results show summary information with mutation counts and frequencies. The gene summary page provides a mutation spectrum map and external resources; the phenotype (tissue) summary page provides lists of mutated genes.

Examples

The figure shows the

CDKN2A ''CDKN2A'', also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins, including the INK4 f ...

gene, which is a tumor suppressor that leads to cancer when it is inactivated.

The COSMIC database contains thousands of somatic mutations that are implicated in the development of cancer. The database collects information from two major sources. Firstly, mutations in known cancer genes are collected from the literature. The list of genes that undergo manual curation are identified by their presence in the Cancer Gene Census. Secondly, data for inclusion in the database is collected from whole genome resequencing studies of cancer samples undertaken by the Cancer Genome Project. For example, Campbell and colleagues used next generation sequencing to examine samples from two individuals with

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

which led to the identification of 103 somatic DNA rearrangements. COSMIC also catalogues mutational signatures in human cancer through the COSMIC Signatures group, which represents a collaboration between COSMIC, the

Wellcome Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit organisation, non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is l ...

, and the

University of California, San Diego The University of California, San Diego (UC San Diego in communications material, formerly and colloquially UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California, United States. Es ...

. The COSMIC signatures database has been leveraged to catalogue the prevalence of specific mutational signatures in human cancer, such as the frequency of ultraviolet radiation-mediated mutagenesis in skin cancers.

References

External links

Catalogue Of Somatic Mutations In Cancer
homepage
IARC TP53 databaseCancer genome anatomy project at the National Cancer InstituteAtlas of Genetics and Cytogenetics in Oncology and HaematologyMethyCancer, a database of human DNA methylation and cancer

COSMIC in the bioinformatics.ca Links Directory
{{Wellcome Trust Cancer genome databases Cancer research Genetic engineering in the United Kingdom Medical databases in the United Kingdom Medical genetics in the United Kingdom Science and technology in Cambridgeshire South Cambridgeshire District Wellcome Trust

Creation and history

Process

Examples

Contents

See also

References

External links