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Benjamin A. Pierce
GENETICS
A Conceptual Approach
FIFTH EDITION
CHAPTER 23
Cancer Genetics
© 2014 W. H. Freeman and Company
23.1 Cancer Is a Group of Diseases
Characterized by Cell Proliferation
•Tumor Formation
•Cancer as a Genetic Disease
•The Role of Environmental Factors in Cancer
****Hallmarks of Pathways to Malignant
Cancer
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Cancer cells acquire self-sufficiency in the signaling processes
that stimulate division and growth.
Cancer cells are abnormally insensitive to signals that inhibit
growth.
Cancer cells can evade programmed cell death.
Cancer cells acquire limitless replicate potential.
Cancer cells develop ways to nourish themselves by stimulating
angiogenesis.
Cancer cells acquire the ability to invade other tissues and
colonize them (metastasize).
Tumor Formation: A Distinct Mass of
Abnormal Cells
• Benign tumor: the tumor remains localized.
• Malignant tumor: tumor cells invade other
tissues.
• Metastasis: the tumor cells induce secondary
tumors.
Cancer as a Genetic Disease
• Genetic evidence for cancer
− Carcinogens, chromosomal abnormalities, inheritance
• Knudson’s multistep model of cancer
− Requires several mutations
• The clonal evolution of tumors
− Tumor cells acquire more mutations that allow them
to become increasingly more aggressive in their
proliferate properties.
Role of Environmental Factors in Cancer
• Cancer is a genetic disease, but most are not
inherited
• Different cancer incidence in different parts of
the world (Table 23.2)
• Factors contributing to cancer (Table 23.3):
– Tobacco use
– Obesity
– Alcohol
– UV radiation
23.2 Mutations in a Number of Different
Types of Genes Contribute to Cancer
•Oncogenes and Tumor-Suppressor Genes
•Genes That Control the Cycle of Cell Division
•DNA-Repair Genes
•Genes That Regulate Telomerase
•Genes That Promote Vascularization and the Spread of Tumors
•MicroRNAs and Cancer
•The Cancer Genome Project
Oncogenes and Tumor-Suppressor
Genes
• Oncogenes: mutated, dominant-acting
stimulatory genes that cause cancer
– Proto-oncogenes: responsible for basic cellular
functions in normal cells; when mutated, they become
oncogenes
• Tumor-suppressor genes: mutated recessiveacting inhibitory genes that are inactive
– Loss of heterozygosity
Mutations in Genes That Control the
Cycle of Cell Division
•Control of the cell cycle
•Cyclin-dependent kinases (CDKs), cyclins
•G1-to-S transition
•Retinoblastoma protein (RB)
•G2-to-M transition
•Mitosis-promoting factor (MPF)
•Spindle assembly checkpoint
•Mutations in cell-cycle control and cancer
•http://www.tankonyvtar.hu/hu/tartalom/tamop425/0011_1A_Molekularis_terapiak_en_book/ch11.ht
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•http://www.discoverymedicine.com/Joana-D-Amaral/2010/02/20/the-role-of-p53in-apoptosis/
Concept Check 1
What would be the most likely effect of a mutation
that caused cyclin B to be unable to bind to CDK?
a. Cells pass through the G2/M checkpoint and enter mitosis
even when DNA has not been replicated.
b. Cells never pass through the G1/S checkpoint.
c. Cells pass through mitosis more quickly than unmutated
cells do.
d. Cells fail to pass through the G2/M checkpoint and do not
enter into mitosis.
Concept Check 1
What would be the most likely effect of a mutation
that caused cyclin B to be unable to bind to CDK?
a. Cells pass through the G2/M checkpoint and enter mitosis
even when DNA has not been replicated.
b. Cells never pass through the G1/S checkpoint.
c. Cells pass through mitosis more quickly than unmutated
cells do.
d. Cells fail to pass through the G2/M checkpoint and do not
enter into mitosis.
Mutations in Genes That Control the
Cycle of Cell Division
•Signal-transduction pathways
− Signals trigger a cascade of intracellular reactions
producing a specific response
− Ras protein
•Receptors
Concept Check 2
Ras proteins are activated when they
.
a.
b.
c.
d.
bind GTP
release GTP
bind GDP
undergo acetylation
Concept Check 2
Ras proteins are activated when they
.
a.
b.
c.
d.
bind GTP
release GTP
bind GDP
undergo acetylation
Mutations in Genes That Control the
Cycle of Cell Division
•DNA-Repair Genes
•Genes That Regulate Telomerase
•Genes That Promote Vascularization and the Spread
of Tumors
•MicroRNAs and Cancer
•The Cancer Genome Project
Concept Check 3
Which type of mutation in telomerase could be
associated with cancer cells?
a. mutations that produce an inactive form of
telomerase
b. mutations that decrease the expression of
telomerase
c. mutations that increase the expression of
telomerase
d. All of the above.
Concept Check 3
Which type of mutation in telomerase could be
associated with cancer cells?
a. mutations that produce an inactive form of
telomerase
b. mutations that decrease the expression of
telomerase
c. mutations that increase the expression of
telomerase
d. All of the above.
23.3 Epigenetic Changes Are Often
Associated with Cancer
• Alterations to DNA methylation or chromatin
structure are seen in many cancers
− Hypermethylation or hypomethylation
• Reversible and not a mutation
23.4 Colorectal Cancer Arises Through the
Sequential Mutation of a Number of Genes
• Excellent example of sequential mutation
• Led to tumor progression model
23.5 Changes in Chromosome Number and
Structure Are Often Associated with Cancer
• Chromosomal instability is a general feature
of cancer cells
− Deletions, inversions and translocations
− Example: a reciprocal translocation between
chromosome 9 and 22 causes chronic myelogenous
leukemia.
− Aneuploidy
23.6 Viruses Are Associated with Some
Cancers
• Retroviruses cause cancer by
− mutating and rearranging proto-oncogenes
− inserting strong promoters near protooncogenes
• Human papilloma virus and cervical
cancer