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Oncogenes and Tumor Suppressor Genes

Chapter:
Nomenclature
Author(s):

Harriet S. Meyer

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 leukemia virus

Abl1, Abl2

Abl1, Abl2

abl

bcl-2

BCL2

BCL2

B-cell CLL/lymphoma 2

Bcl2

Bcl2

bcl

erb

ERBB2, ERBB3, ERBB4,

ERBB2, ERBB3, ERBB4

avian erythroblastic leukemia

Erbb2, Erbb3, Erbb4,

Erbb2, Erbb3, Erbb4

erb

ets

ETS1, ETS2

ETS1, ETS2

avian erythroblastosis

Ets1, Ets2

Ets1, Ets2

ets

fes

FES

FES

feline sarcoma

Fes

Fes

fes

fms

CSF1R (formerly FMS)

colony stimulating factor 1 receptor

McDonough feline sarcoma

Csf1r(formerly Fms)

(CSF1R)

fos

FOS, FOSB

FOS, FOSB

murine osteosarcoma

Fos, Fosb

Fos, Fosb

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 sarcoma virus

Mos

Mos

mos

myb

MYB

MYB

avian myeloblastosis

Myb

Myb

myb

myc

MYC

MYC

avian myelocytomatosis

Myc

Myc

myc

raf

RAF1, ARAF, BRAF

RAF1, ARAF, BRAF

murine leukemia

Raf1, Araf, Braf

Raf1, Araf1, Braf

raf

ras

family with many human homologues, eg, HRAS, NRAS, RAB9A, RRAS, RRAS2

HRAS1, NRAS, RAB9A, RRAS, RRAS2

retrovirus-associated DNA sequence

Hras1, Nras, Rab9, Rras, Rras2

Rab9A, Rras, Rras2, Hras, Nras, Rab9

ras

sis

PDGFB

PDGFB (platelet-derived growth factor, B chain)

simian sarcoma virus

Pdgfb

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.

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