基因突變數(shù)據(jù)庫介紹

1、Xinsen Xu, MDDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xian Jiaotong UniversityDatabases for cancer gene mutationsMarch 22, 2012Cancers are caused by accumulated mutations in various genes and consequent functional alterations of proteins. The majority of cance

2、rs occur sporadically in individuals. These are thought to be the result of multistep tumorigenesis, during which somatic mutations occur in a series of genes that play important roles in the regulation of growth, differentiation and apoptosis. However, some cancers occur rarely but repeatedly in di

3、fferent members of the same family, and this is considered to be familial cancer in which germline mutations are known to be involved. Accumulated Mutations In Various GenesThe changes in nucleotide sequences and expression patterns of cancer-related genes are being extensively studied to better und

4、erstand the mechanisms of tumorigenesis. At present, a number of computer databases for molecular information on cancer-related genes are available publicly through the internet. A Number of DatabasesLocus-Specific Mutation Database and Central Mutation DatabaseLocus-Specific Mutation Database (LSDB

5、) and Central Mutation DataBase (CMDB). LSDB basically deals with a particular gene (genetic locus) that is known to be involved in the pathogenesis of a certain disease.There are 571 LSDBs. The genes responsible for familial cancers and cancer-related genes have been important targets of LSDBs. CMD

6、B is an integrated database for multiple genes, which facilitates searches across genes. In the ideal CMDB, all mutation data for known disease genes would be collected with one common database format, and the user interface must be unified in a visual manner by effective use of graphics. Databases

7、specialized for cancers-IARC TP53 Mutation DatabaseCreated by the International Agency for Research on Cancer (IARC) at Lyon, France, since 1994Available data sets include TP53 somatic mutations in sporadic cancers, TP53 germline mutations in familial cancers, TP53 polymorphisms identifiedin human p

8、opulations, functional properties of TP53 mutant proteins, and TP53 gene status in human cell lines. Data entries in the latest version are 27580 somatic mutations reported in 1876 original publications, 597 germline mutations reported in 129 publications (1989 up to date) and functional properties

9、of more than 425 mutant proteins. Databases specialized for cancers-IARC TP53 Mutation Database Databases specialized for cancers-IARC TP53 Mutation DatabaseHuman TP53 coding sequence with exon boundaries in blue and CpG sites in red. Ref sequence: SwissProt #P04637. Databases specialized for cancer

10、s-Universal Mutation DatabasesUniversal Mutation Databases (UMDs) are LSDBs constructed using a UMD software package. UMDs include mutations of cancer-related genes such as TP53, APC, BRCA1, BRCA2, MEN1 and VHL. UMDs also include mutations of other genes such as FBN1, LDLR, LMNA, EMD and ATP7B, whic

11、h are responsible for genetic diseases.The UMD package contains various software tools to dynamically linkamong LSDBs, with a database structure suitable for collecting and analyzing a wide range of clinical data. Databases specialized for cancers-Universal Mutation Databases Databases specialized f

12、or cancers-COSMICThe Catalog of Somatic Mutations in Cancer (COSMIC) was developed by The Sanger Center to provide integrated genetic data for cancer genes.COSMIC contains various information on definite cases of cancer tissues and cell lines, such as tissue/cell line ID, derived organ, tissue or ca

13、ncer subtype, analyzed gene name, and mutation details. It is possible to display mutation position and frequency, and to list genes with mutations for particular cancer cases. The current data contents (version 21, released 14 September 2006) are: 3611 references; 164 905 cancer tissues and cell li

14、nes; 1339 tested genes; 86 cancer genes with mutations; and 344 cancer-related genes with mutations. Databases specialized for cancers-COSMIC Databases specialized for cancers-COSMIC Databases specialized for cancers-COSMIC Databases specialized for cancers-COSMIC Databases specialized for cancers-C

15、OSMIC Databases specialized for cancers-COSMIC Databases specialized for cancers- Atlas of Genetics and Cytogenetics in Oncology and Haematology A database for genetic and cytogenetic information on cancer, leukemia and cancer-prone diseases such as xeroderma pigmentosum and LiFraumeni syndrome. The

16、 contents include clinical characteristics, associated chromosomal abnormalities, and various information on the responsible genes. The numbers of collected genes are approximately 900 for cancer genes and 3600 for possible cancer-related genes. Databases specialized for cancers-CGAP The Cancer Geno

17、me Anatomy Project (CGAP) is a project run by the National Cancer Institute, USA, and the National Center for Biotechnology Information (NCBI), USA, to determine the gene expression profiles of normal, precancer and cancer cells. The website of this project consists of seven modules: genes, tissues,

18、 pathways, RNA interference (RNAi), chromosomes, SAGE Genie and tools. Databases specialized for cancers- Tumor Gene DatabaseThe Tumor Gene Database has been maintained at the Baylor College of Medicine (USA).The database collects various information on the proto-oncogenes and tumor suppressor genes

19、 that are targets for cancer-causing mutations. The information in this database is categorized into 2030 groups such as clinical, DNA structure, function, oncogenicity, protein binding, protein structure and tumor type. Databases with CMDB-like characteristics-Online Mendelian Inheritance in ManMen

20、delian Inheritance in Man (MIM) is an encyclopedia of human genetic traits written by Professor Victor A. McKusick (Johns Hopkins University) in1966. It has been edited continuously and is currently in its 12th edition. Genetic traits in this book include hereditary diseases such as hemophilia and f

21、amilial cancers, non-disease but inherited traits such as blood groups, and various genes with known function. Online Mendelian Inheritance in Man (OMIM) is a web-based computer search system of MIM, which is available through the NCBI, USA. The number of entries regarding cancer is more than 250, most of which are familial cancers. Databases with CMDB-like c