Oncogenes and Tumor Suppressor Genes
15.6.3 Oncogenes and Tumor Suppressor Genes
- Cancer is caused by an accumulation of genetic
- alterations that confer a survival advantage
- to the neoplastic cell.
- J. L. Jameson1(p73)
Oncogenes:
Oncogenes are “[g]enes that normally play a role in growth but, when overexpressed or mutated, can foster the growth of cancer.”2 Oncogenes were discovered and characterized in viruses and animal experimental systems. These genes exist widely outside the systems in which they were discovered, and their normal cellular homologues are important in cell division and differentiation.
Human oncogenes should be expressed according to style for human gene symbols (see 15.6.2, Human Gene Nomenclature). Mouse oncogenes (and other nonhuman oncogenes) should be expressed according to style for mouse gene symbols (see 15.6.5, Nonhuman Genetic Terms). Retroviral oncogenes are expressed in a style typical of microbial genes (see 15.6.5, Nonhuman Genetic Terms), namely, 3 letters, italicized, lowercase. The protein products of the oncogenes (oncoproteins) typically use the same term as the oncogene but in roman type. In humans, the protein is all capitals; in mice, the protein has an initial capital.
Retroviral Oncogenes |
Human Gene Homologue(s); Mouse Gene Homologue(s) |
Human Protein Product(s); Mouse Protein Product(s); Retroviral Oncoprotein |
Origin |
|---|---|---|---|
abl |
ABL1, ABL2 |
Abl1, Abl2 |
Abelson murine |
ABL1, ABL2 |
Abl1, Abl2 |
leukemia virus |
|
abl |
|||
bcl-2 |
BCL2 |
Bcl2 |
B-cell |
BCL2 |
Bcl2 |
CLL/lymphoma 2 |
|
bcl |
|||
erb |
ERBB2, ERBB3, |
ERBB2 ERBB3, |
avian erythroblastic |
ERBB4, |
ERBB4 |
leukemia |
|
Erbb2, Erbb3, |
Erbb2 |
||
Erbb4 |
Erbb3, Erbb4 |
||
erb |
|||
ets |
ETS1, ETS2 |
Ets1, Ets2 |
avian |
Ets1, Ets2 |
Ets1, Ets2 |
erythroblastosis |
|
ets |
|||
fes |
FES |
FES |
feline sarcoma |
Fes |
Fes |
||
fes |
|||
fms |
CSF1R (formerly FMS) |
colony stimulating |
McDonough |
Csf1r(formerly Fms) |
factor 1 receptor |
feline sarcoma |
|
(CSF1R) |
|||
fos |
FOS, FOSB |
FOS, FOSB |
murine |
Fos, Fosb |
Fos, Fosb |
osteosarcoma |
|
fos |
|||
jun |
JUN, JUNB, JUND |
JUN, JUNB, JUND |
avian sarcoma |
Jun, Junb, Jund |
Jun, Junb, Jund |
||
jun |
|||
kit |
KIT |
Kit |
feline sarcoma |
Kit |
Kit |
||
kit |
|||
mos |
MOS |
Mos |
Moloney |
Mos |
Mos |
sarcoma virus |
|
mos |
|||
myb |
MYB |
MYB |
avian |
Myb |
Myb |
myeloblastosis |
|
myb |
|||
myc |
MYC |
MYC |
avian |
Myc |
Myc |
myelocytomatosis |
|
myc |
|||
raf |
RAF1, ARAF, |
RAF1, ARAF, |
murine leukemia |
BRAF |
BRAF |
||
Raf1, Araf, Braf |
Raf1, Araf1, Braf |
||
raf |
|||
ras |
family with |
HRAS1, NRAS, |
retrovirus- |
many human |
RAB9A, RRAS, |
associated |
|
homologues, |
RRAS2 |
DNA sequence |
|
eg, HRAS, NRAS, |
Rab9A, Rras, Rras2 |
||
RAB9A, RRAS, |
Hras1, Nras, Rab9 |
||
RRAS2 |
ras |
||
Hras, Nras, Rab9 |
|||
Rras, Rras2 |
|||
sis |
PDGFB |
PDGFB |
simian sarcoma |
Pdgfb |
(platelet-derived growth factor, B chain) |
virus |
|
Pdgfb |
|||
sis |
|||
src |
SRC |
SRC |
Rous sarcoma virus |
Src |
Src |
||
src |
Examples of use are as follows:
ras activation and inactivation
The ras protein, ras, functions as a signaling molecule.
HER2/neu.
The symbol for the oncogene known as HER2/neu is actually ERBB2. HER2 (from human epidermal growth factor receptor 2) and NEU have been shown to be the same as ERBB23,4 and are current aliases for ERBB2.5 Because the term HER2/neu is widely used and recognized, it may be included in parentheses after the first mention of ERBB2:
ERBB2(formerly HER2 or HER2/neu)
Commonly, the oncogene term contains a prefix that indicates the source or location of the gene: v- for virus or c- for the oncogene’s cellular or chromosomal counterpart. The c- form is also known as a proto-oncogene and in standard gene nomenclature (see 15.6.2, Human Gene Nomenclature) is given in all capitals, as in the human gene homologues column of the tabulation above and the following examples:
c-abl (ABL1) |
c-mos (MOS) |
v-abl |
v-mos |
Editors should not substitute one type of term for another.
The protein product may be similarly prefixed:
c-abl |
c-mos |
v-abl |
v-mos |
Additional prefixes may further identify oncogenes. Expansions of some prefixes are given below, but it should not be inferred that the gene in question is associated only with the tumor it is named for:
Oncogene |
Prefix Expansion |
|---|---|
B-lym |
B-cell lymphoma |
L-myc |
small cell lung carcinoma |
N-myc |
neuroblastoma |
H-ras |
Harvey rat sarcoma |
c-H-ras |
|
v-H-ras |
|
K-ras |
Kirsten rat sarcoma |
c-K-ras |
|
v-K-ras |
|
N-ras |
neuroblastoma |
For example:
Hypothesis: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the superior mesenteric artery.
Numbers or letters designate genes in a series, eg:
K-ras-2
H-ras-1
erb-b2
Fusion Oncogenes and Oncoproteins.
The result of fusion of an oncogene and another gene is known as a fusion oncogene. The product of a fusion oncogene is a fusion oncoprotein. Terms for fusion oncogenes and their products may use traditional oncogene format or standard human gene format, as in the following examples:
Fusion Oncogene |
Fusion Oncoprotein |
Explanation |
|---|---|---|
bcr-abl |
bcr-abl |
bcr: breakpoint cluster region |
c-fos/c-jun |
c-fos/c-jun |
|
gag-onc |
gag-onc |
general term for fusion proteins of viral gag (group-specific antigen) gene and oncogene |
gag-jun |
gag-jun |
|
PML-RARA |
PML-RARα |
promyelocytic leukemia-retinoic acid α |
Tumor Suppressor Genes.
Tumor suppressor genes are “[g]enes that normally restrain cell growth but, when missing or inactivated by mutation, allow cells to grow uncontrolled.”6 Examples are in the tabulation below:
Gene |
Gene Product |
Explanation |
|---|---|---|
CDKN1A |
p21 |
cyclin-dependent kinase (CDK) inhibitor 1A |
CDKN1B |
p27 |
CDK inhibitor 1B |
CDKN1C |
p57 |
CDK inhibitor 1C |
DCC |
a transmembrane receptor protein |
deleted in colorectal carcinoma |
GLTSCR1 |
glioma tumor suppressor candidate region gene 1 |
|
NF1 |
neurofibromin 1 |
|
RB1 |
Rb protein |
retinoblastoma 1 |
TP53 |
p53 |
a 53-kd protein |
WT1 |
a zinc finger protein |
Wilms tumor 1 |
References
1. Jameson JL. Oncogenes and tumor suppressor genes. In: Jameson JL, Collins FS. Principles of Molecular Medicine. Totowa, NJ: Humana Press; 1998:73-82.
Find This Resource
2. Terms and definitions (O). National Institutes of Health Office of Rare Diseases. http://ord.aspensys.com/asp/resources/glossary_n-r.asp#O. Accessed April 21, 2006.
3. V-ERB-B2 avian erythroblastic leukemia viral oncogene homolog 2; ERBB2. OMIM. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164870. Updated January 30, 2006. Accessed April 21, 2006.
4. Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR, Aaronson SA. erb B-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987;237(4811):178-182.
Find This Resource
5. Searchgenes. Human Gene Nomenclature Database Search Engine. http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl. Updated April 21, 2006. Accessed April 21, 2006.
6. Terms and definitions (T). National Institutes of Health Office of Rare Diseases. http://ord.aspensys.com/asp/resources/glossary_s-z.asp#T. Accessed April 21, 2006.