5.9 years ago by

Malachi Griffith ♦16k

Washington University School of Medicine, St. Louis, USA

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• The Gene Ontology used to have a term 'Tumor Suppressor' but this has been superseded by the term 'regulation of cell cycle'.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

4.8 years ago by

Travis • 2.7k

USA

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.

TSGene: http://bioinfo.mc.vanderbilt.edu/TSGene/

5.9 years ago by

Sean Davis ♦ 23k

National Institutes of Health, Bethesda, MD

An additional resource is the NCI Cancer Gene Index.

5.8 years ago by

Obi Griffith ♦ 16k

Washington University, St Louis, USA

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?

3.7 years ago by

Obi Griffith ♦ 16k

Washington University, St Louis, USA

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.

5.7 years ago by

Jiri Voller • 20

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....

4.7 years ago by

henryvuong • 700

USA

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

11 months ago by

Min • 60

http://ongene.bioinfo-minzhao.org/ The literature based oncogene list, the same author of TSGene.

5.9 years ago by

Larry_Parnell ♦16k

Boston, MA USA

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.