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A census of human cancer genes

Key Points

  • We have conducted a census from the literature of genes that are mutated and causally implicated in cancer development ('cancer genes').

  • So far, 291 cancer genes have been reported, more than 1% of all the genes in the human genome.

  • 90% of cancer genes show somatic mutations in cancer, 20% show germline mutations and 10% show both.

  • The most common mutation class among the known cancer genes is a chromosomal translocation that creates a chimeric gene or apposes a gene to the regulatory elements of another gene.

  • Many more cancer genes have been found in leukaemias, lymphomas and sarcomas than in other types of cancer, despite the fact that they represent only 10% of human cancer. These genes are usually altered by chromosomal translocation.

  • The most common domain that is encoded by cancer genes is the protein kinase. Several domains that are involved in DNA binding and transcriptional regulation are common in proteins that are encoded by cancer genes.

Abstract

A central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis ('cancer genes'). After two decades of searching, how many have been identified and how do they compare to the complete gene set that has been revealed by the human genome sequence? We have conducted a 'census' of cancer genes that indicates that mutations in more than 1% of genes contribute to human cancer. The census illustrates striking features in the types of sequence alteration, cancer classes in which oncogenic mutations have been identified and protein domains that are encoded by cancer genes.

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Figure 1: Mutation types in human cancer.
Figure 2: Proportion of translocated genes in human cancer.
Figure 3: Dominant and recessive mutations in human cancer.
Figure 4: Proportion of genes associated with different tumour types.

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Author information

Affiliations

Authors

Corresponding author

Correspondence to Michael R. Stratton.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Related links

Related links

DATABASES

Cancer.gov

breast cancer

colorectal cancer

lung cancer

LocusLink

APC

ATM

BMPR1A

BRCA1

BRCA2

CBP

CDK4

CDKN2A

CHK2

EGFR

EP300

ETV6

FHIT

FLT3

HRAS

KIT

MET

MLH1

MLL

NTRK3

NTRK1

PAX8

PDGFRA

PRCC

PPARγ

PRKAR1A

PTEN

RET

RUNXBP2

STK11

TFE3

TGF-β

TGF-βRII

TP53

WWOX

OMIM

Carney complex

Peutz–Jegher syndrome

FURTHER INFORMATION

Cancer Genome Project

Ensembl Human Genome Browser web site

Pfam home page

Wellcome Trust Sanger Institute web site

Glossary

CpG ISLANDS

GC-rich areas of the genome, usually of the order of a kilobase in size, often in and around the 5′ regions of genes, which retain an unusually high number of CpG dinucleotides.

PASSENGER OR BYSTANDER MUTATIONS

Somatic mutations that are found in cancer cells that are not involved in generating the neoplastic phenotype.

MYXOMA

A rare type of tumour that is usually composed of sparse mesenchymal cells interspersed amid large amounts of intercellular material.

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Futreal, P., Coin, L., Marshall, M. et al. A census of human cancer genes. Nat Rev Cancer 4, 177–183 (2004). https://doi.org/10.1038/nrc1299

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