Biology of Disease

family of oncogenes. The mutation of a proto-oncogene to form an oncogene
usually results in the production of a protein that has increased activity, or in
the synthesis of greater than normal amounts of the protein, as, for example,
when the gene is continually active. Such mutations are otherwise known
as ‘gain-of-function’ mutations. Oncogenes were first discovered in certain
viruses that cause cancer (Section 17.5). Some viruses which cause cancer
have a gene that is the equivalent of a cellular proto-oncogene. These genes
are thought to have been derived initially from host DNA into which the viral
DNA was integrated and to have undergone mutation during viral passage.
When DNA derived from the virus becomes inserted into the host genome,
the viral oncogene may provide the additional signal for cellular proliferation,
or may override the normal cellular controls, resulting in the unregulated
division of infected cells. The viral and cellular forms of the oncogene are
usually distinguished by the prefix ‘v’ and ‘c’ respectively as in, for example,
v-MYC andc-MYC.

Some examples of oncogenes and associated tumors are shown in Table 17.2.

Margin Note 17.2 Gene E2F3

The gene E2F3, which is associated

with the development of prostate

cancer (Section 17.8), was discovered

in 2004. The gene encodes a protein

that controls cell division. It is

produced in appropriate amounts in

healthy prostate cells but is

overexpressed in prostate cancer

cells, leading to their excessive

proliferation. The discovery is useful

because this protein can be used as a

marker for the more aggressive forms

of prostate cancer, allowing treatment

to be tailored and monitored

appropriately.

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Proto-oncogene Codes for Disease

ERB-B1 epidermal growth factor

receptor (EGFR)

squamous cell carcinoma of the lung

ERB-B2 (HER-2) growth factor receptor breast cancer

ovarian cancer

cancer of the salivary gland

H-RAS GTPase bladder cancer

stomach cancer

breast cancer

thyroid cancer

and others

K-RAS GTPase stomach cancer

pancreatic cancer

melanoma

bladder cancer

neuroblastoma

thyroid cancer

and others

BCR-ABL tyrosine kinase chronic myelogenous leukemia

acute lymphoblastic leukemia

SRC tyrosine kinase colon cancer

MYC transcription factor breast, stomach and lung cancer

leukemias

FOS transcription factor lung cancer

breast cancer

Table 17.2Some oncogenes and associated tumors

Tumor Suppressor Genes

Tumor suppressor genes, in contrast to proto-oncogenes, encode proteins
that inhibit the proliferation of cells that contain deleterious mutations.
Mutations in the tumor suppressor genes themselves may then lead to a
loss of this inhibition that is, they are ‘loss of function’ mutations. Some
examples of tumor suppressor genes are the TP53 gene, the retinoblastoma
susceptibility gene, RB, and the Wilms’ tumor gene, WT1. The TP53 gene is

MOLECULAR BIOLOGY OF CANCER

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY ),.

Margin Note 17.3 EMSY and

breast cancer

EMSYis a gene involved in regulating

the expression of other genes involved

in the repair of DNA. It appears to

have a role in the development of

breast cancer. In 2003, an analysis of

more than 500 breast cancers and

over 300 ovarian cancers showed

that multiple copies of this gene were

present in 13% of breast cancers

and 17% of ovarian cancers. Women

whose tumors carried multiple cop-

ies of the gene survived on average

for six years after diagnosis whereas

those with normal amounts of the

gene had a mean survival time of 14

years. Thus, the presence of multiple

copies is associated with an aggres-

sive form of breast cancer and a poor

prognosis.

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