Essential Cell Biology 5th edition

724 CHAPTER 20 Cell Communities: Tissues, Stem Cells, and Cancer
Figure 20–46 Genes that are critical
for cancer are classified as protooncogenes
or tumor suppressor
genes, according to whether the
dangerous mutations are dominant
or recessive. (A) Oncogenes act in a
dominant manner: a gain-of-function
mutation in a single copy of the protooncogene
can drive a cell toward
cancer. (B) Loss-of-function mutations
in tumor suppressor genes generally
act in a recessive manner: the function
of both copies of the gene must be
lost to drive a cell toward cancer. In this
diagram, normal genes are represented
by light blue squares, activating
mutations by red rays, and inactivating
mutations by hollow red squares.
(A) dominant mutation (gain of function)
normal cell
MUTATION INACTIVATES
ONE COPY OF TUMOR
SUPPRESSOR GENE
tumor suppressor
gene
normal cell
MUTATION IN ONE COPY OF PROTO-ONCOGENE
CREATES ONCOGENE
proto-oncogene
(B) recessive mutation (loss of function)
no effect of
mutation in one
gene copy
SECOND MUTATION
INACTIVATES
SECOND GENE
COPY
hyperactive oncogene
complete loss of
tumor suppressor
gene activity
excessive cell
survival,
proliferation,
or both
excessive cell
survival,
proliferation,
or both
mutations have a dominant effect: only one gene copy needs to be
mutated to promote the development of cancer. The resulting mutant
gene is called an oncogene, and the corresponding normal form of the
gene is called a proto-oncogene (Figure 20–46A). Figure 20–47 shows
a variety of ways in which a proto-oncogene can be converted into its
corresponding oncogene.
For other cancer-critical genes, the danger lies in mutations that destroy
their activity. These loss-of-function mutations are generally recessive:
both copies of the gene must be lost or inactivated to contribute to cancer
development; the normal gene is called a tumor suppressor gene
(Figure 20–46B). In addition to such genetic alterations, tumor suppressor
genes can also be silenced by epigenetic changes, which alter gene
expression without changing ECB5 e20.48-20.49
the gene’s nucleotide sequence (as discussed
in Chapter 8). Epigenetic changes are thought to silence some
tumor suppressor genes in most human cancers. Figure 20–48 highlights
a few of the ways in which the activity of a tumor suppressor gene can
be lost.
proto-oncogene
MUTATION
IN CODING SEQUENCE
GENE AMPLIFICATION
CHROMOSOME REARRANGEMENT
DNA
or
DNA
RNA
RNA
protein
hyperactive mutant
protein made in
normal amounts
normal protein overproduced
nearby regulatory
DNA sequence causes
normal protein to
be overproduced
fusion with actively
transcribed gene
produces hyperactive
fusion protein
Figure 20–47 Several kinds of gain-of-function mutations can convert a proto-oncogene into an oncogene. In each case, the
change leads to an increase in the gene’s function.