https://www.biostars.org/p/15890/
Does anyone know of a good source of human genes that act as a tumor suppressor or oncogene? The source can be a database or data mining approach that queries a more general database.
Some possible features of a 'good' source:
- More than just a list of 'cancer genes'. One abstract with the name of the gene and the word cancer in it does not make it a convincing cancer gene. But a more sophisticated text-mining based approach would be acceptable
- The gene will be annotated as a tumor suppressor or oncogene with additional information on how this classification is justified
- Other relevant annotation such as whether the gene is involved in DNA repair, apoptosis, etc.
- Up to date. A spreadsheet from 10 years ago is less useful than a routinely updated source.
- Free and open source. Although if you know of commercial options please suggest them.
Here are some of the things I have found so far:
- The Wikipedia entries above list categories of oncogenes .. but not all RTKs for example will necessarily act as an oncogene
- The Gene Ontology used to have a term 'Tumor Suppressor' but this has been superseded by the term 'regulation of cell cycle'. A gene involved in regulation of the cell cycle may generally have the potential to function as a tumor suppressor but it would be nice to know which had been demonstrated to do so and how. A combination of GO terms and evidence codes might be acceptable if someone wishes to elaborate on this approach
- UniProtKB has a keyword 'Proto-oncogene' associated with 560 genes and a keyword 'Tumor Suppressor' associated with 631 genes.
- A compilation of cancer gene lists from the 'Bushman Lab'
- The Sanger Cancer Gene Census
- A more empirical approach might involve using patterns of somatic mutation across many cancers to identify likely tumor suppressors and oncogenes. Where tumor suppressors are expected to be characterized by loss-of-function mutations (copy number deletions, nonsense, or missense mutations spread across multiple sites in the gene) and oncogenes would be characterized by recurrent mutation sites (amplifications, mutation hotspots, gene fusions involving a particular gene partner, etc.). COSMIC is already working along these lines but if there are others, please post.
- The Cancer HotSpots Resource performs an analysis that looks for recurrently mutated cancer hotspots by mining tumor sequence data. These hotspots can be indicative that a gene is an Oncogene.
- A variety of older websites that list tumor suppressors: TSGDB, Tumor Gene Database, and TAG
Useful suggestions gathered from below (refer there for more details):
- Network of Cancer Genes
- NCI Cancer Gene Index
- Table of oncogenes and tumor suppressor genes from Vogelstein et al. 2013
- MSKCC Cancer Genes Via Gene Ranker
- TSGene from Vanderbilt
Sources you could mine to develop your own lists:
- ICGC data portal
- TCGA data portal
- MSKCC cBioPortal
- IntOGen, Integrative Oncogenomics
- Broad, Tumor Portal
- Genomic Data Portal
Organizations that are annotating druggable/actionable genes:
- Washington University Genome Institute: DGIdb, DOCM, CIViC
- MD Anderson: PCT
- Vanderbilt: MyCancerGenome
- Dienstmann lab: GDKD
Some relevant posts:
- Web resources to find cancer indication where a given gene is amplified
- Where can I find mutation databases specialized in cancer?
- Where can I find Data sets of cancer publicly available?
- Mutated gene sequence database for breast cancer
- help in obtaining a cancer-related database
- List of known cancer resources
- Learning about cancer from the ground up...
- Sources of information about amplified genes (and overexpressed) in cancer
- Exploring cancer mutation data portals
I realize this is an old thread but still a very relevant question. The following resource ticks most boxes for tumor suppressor genes. It is a recent (NAR) published database resource, complete with literature evidence, downloadable data and a number of nice web-based resources like the ability to view Kegg pathways with tumor suppressors highlighted.
An additional resource is the NCI Cancer Gene Index.
Looks promising. From the website: "The goal of the Cancer Gene Index is to further translational cancer research by providing a high quality data resource consisting of genes that have been experimentally associated with human cancer diseases and/or pharmacological compounds, the evidence of these associations, and relevant annotations on the data. This extremely valuable resource was created through a unique process that coupled automated linguistic text analysis of millions of MEDLINE abstracts with manual validation and annotation of the extracted data by expert human curators."
The Cancer Genes database is produced by MSKCC and has a nice interface with which you can do a very simple query and get a list of 873 tumor suppressor genes and 495 oncogenes with associated gene IDs and GO categories. But it does not meet your criteria for stringency as tumor suppressors are determined by a simple term query of Entrez Gene.
What about text-mining something like OMIM or even the rapidly improving gene pages in Wikipedia. This might get you better quality than going straight at the literature because a lot of manual/expert curation has already been put in. And, if you have a big over-representation of the term "Tumor Suppressor" in an OMIM record or the "Role in Disease" section of a gene's wikipage its probably a decent candidate.
See this OMIM search with genes sorted by relevance.
http://omim.org/search?index=entry&start=1&limit=10&search=tumor+suppressor&sort=score+desc%2C+prefix_sort+desc
Its just too bad that these manually curated resources don't also have more controlled data entry mechanisms where the curators could indicate that it was a tumor suppressor and provide evidence through a controlled vocabulary. Maybe someone is aware of such efforts?
Unfortunately, it seems the Cancer Genes database has gone dark. I have tried several times in recent weeks and always get a 404 error. While searching for its new home I did find this list of cancer genes lists which is used as a gene ranker for GBM. I'm not sure how current it is. I feel like the you might also be able to get at cancer gene lists through the cBio Portal somehow but have not figured out how yet.
The 404 points you at this old paper version:http://nar.oxfordjournals.org/content/35/suppl_1/D721.full
Another option is the Network of Cancer Genes. According to the site, NCG is a:
Manually curated list of 2,000 protein-coding cancer genes and 64 OncomiRs. Cancer genes are genes with a driver role in the onset of human cancer upon mutations of their sequence and/or amplifications of their genomic locus. 537 are known cancer genes from the Cancer Gene Census and from a list of genes that undergo cancer-specific amplifications. Their involvement in cancer is documented in the literature. 1463 are candidate cancer genes that derive from the manual curation of 77 whole genome or whole exome cancer-resequencing screenings. Their involvement in cancer is inferred with various statistical methods.
NCI Cancer Gene Index looks great, seems that a lot of effort was invested into curation of mined cancer related sentences. But the problem is that the project ended in 2009. In fact I got here, when I was looking for its successors....
There is a nice table of oncogenes and tumor suppressor genes from this publication (Supplementary material) Vogelstein, B., Papadopoulos, N., Velculescu, V., Zhou, S., Diaz, L. & Kinzler, K. Cancer genome landscapes. Science (New York, N.Y.) 339, 1546–58 (2013).http://www.sciencemag.org/content/339/6127/1546.full
http://ongene.bioinfo-minzhao.org/ The literature based oncogene list, the same author of TSGene.
The NCI Cancer Gene Index is good +1. This was developed with software from Biomax and you can find information about the collaboration between NCI and Biomax as well as details on the dataset here.
Anyone knows how to get this list of tumour suppressor genes from NCI Cancer gene index? I've been reading and trying but the interface of searching is not really firendly
I feel like, right now, the best answer to this question is the Cancer Gene Census. They currently provide a TSV download of their complete list of 567 genes with nearly all being indicated as oncogene and/or tumor suppressor (TSG).
I doubt that you have missed a useful resource given your fairly extensive groundwork. Interesting questions though, particular if there is no good solution to the problem yet.
haha I compiled that "Bushman Lab" list back in 2005. NCI was very disorganized - there was no Cancer Gene Index or lists to speak of. Today I think it would almost be easier to assemble a list of "non-cancer genes", since there are so many passenger mutations that can occur.
Yeah the passenger mutation comment is a good one. This is why I am interested in more context. As you say, virtually every gene cited in more than 5 papers is a 'cancer gene' and the remainder just aren't a cancer gene yet. What we need is more information on how each gene is related to cancer initiation, progression, metastasis, response to treatment, etc., etc.