2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
OVERVIEW OF CANCER DISCOVERY ACTIVITIES
This educator guide provides support for two Cancer Discovery activities, both based on a Howard
Hughes Medical Institute 2013 Holiday Lectures on Science video featuring researcher Dr. Charles L.
Sawyers. Students begin by watching the online video clip, Cancer as a Genetic Disease
(http://www.hhmi.org/biointeractive/
cancer-genetic-disease-video-highlights), and completing the accompanying Video Worksheet. After that
assignment, instructors can decide which of the two activities to use in class.
Activity 1: Classifying Cancer Genes
In Activity 1, students identify the locations on chromosomes of genes involved in cancer, or “cancer
genes.” Using the set of 139 Cancer Gene Cards and associated chromosome posters, students discover
the following:
• About 140 human genes are currently known to be involved in cancer.
• Cancer genes are located throughout the human genome.
• The proportion of oncogenes versus tumor suppressor genes is roughly equal.
• The main cellular processes affected by mutations in cancer genes are cell survival, cell fate, and
genome maintenance.
• One way to visualize genetic data is to map genes onto chromosomes.
Activity 2: Examining Cancer Patient Data
In Activity 2, students explore the genetic basis of cancer by examining cards that list genetic mutations
found in the DNA of actual cancer patients. Small-group work spurs discussion about the genes that are
mutated in different types of cancers and the cellular processes that the affected genes control.
Students are asked to identify patterns and trends in the data. Using the Cancer Patient Cards, students
discover the following:
• Cancer is typically caused by mutations in several genes (i.e., two to eight genes for each cancer).
• Patients with cancer have different combinations of mutated genes.
• Mutations in the same genes can be involved in the development of different types of cancers (i.e.,
breast cancer or lung cancer).
• Mutations in different genes can cause the same type of cancer.
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
Figure 1. Planning flowchart for the two Cancer Discovery activities. Instructors may assign one activity or both. Both
activities are based on a video clip that can be assigned as homework in advance of the in-class activity. Activity 1 requires
roughly 35 minutes of class time and Activity 2 roughly 30 minutes. Both activities suggest a concluding class discussion (about
5 minutes) and a 3-2-1 analysis as a follow-up homework assignment.
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
KEY CONCEPTS AND LEARNING OBJECTIVES
• Cancer is a disease of unregulated cell growth and division that interferes with the normal functions
of the body (Activity 1 and 2).
• Cancer is caused by mutations in genes that normally play important functions in cells—in cell
growth and division, cell fate (differentiation), and genome maintenance (Activity 1 and 2).
• By analyzing the genome sequences of many different kinds of cancer, researchers have thus far
identified about 140 genes that, when mutated, contribute to the development of different cancers.
These genes are distributed throughout the genome (Activity 1 and 2).
• Cancer genes can be classified as either tumor suppressor genes or proto-oncogenes/oncogenes
(Activity 1 and 2).
• Tumor suppressor genes act like “brakes” that inhibit cell growth and division. When mutated, they
can lose their braking function, which results in uncontrolled cell growth and division (Activity 1 and
2).
• Proto-oncogenes normally stimulate cell growth and division in a carefully controlled way. Mutated
versions of proto-oncogenes, called oncogenes, act like “accelerators,” causing cells to grow and
multiply uncontrollably (Activity 1 and 2).
• Not all cancers of the same type have the same combination of mutated genes (Activity 2).
• Certain genes are involved in multiple types of cancer (Activity 2).
After completing these activities, students will be able to
• visualize genetic data (Activity 1);
• describe the differences between proto-oncogenes, oncogenes, and tumor suppressor genes in
their own words and using examples (Activity 1 and 2);
• use online databases to determine information about the genes listed in the cancer cards (Activity 1
and 2);
• connect the information in the video clip to the data contained in the Cancer Patient Cards, the
Cancer Gene Cards, or both (Activity 1 and 2); and
• summarize what they have learned and what surprised them, and formulate one outstanding
question (Activity 1 and 2).
CURRICULUM CONNECTIONS
Curriculum Standards
NGSS (April 2013) HS-LS1-1, HS-LS1-2, HS-LS1-4
AP Biology (2012–13) 2.A.3, 2.E.1, 3.A.2, 3.B.2, 3.D.3, 3.D.4, 4.A.3, and SP 5,
6
IB Biology (2016) 3.1, 3.2, 3.4, and Aims 7, 8
KEY TERMS
cancer, cell cycle, cell death, cell fate, differentiation, mutation, oncogene, proto-oncogene, tumor
suppressor gene
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
TIME REQUIREMENTS
Each activity is designed to be completed within one 50-minute class period, provided that the Cancer
as a Genetic Disease video clip (8:30 minutes) and the accompanying Video Worksheet are assigned
beforehand as homework. See Figure 1 for a flowchart outlining the activities.
SUGGESTED AUDIENCE
Both cancer discovery activities are appropriate for first-year high school biology (honors or regular), AP
and IB Biology, and other biology-related electives (i.e., Genetics, Anatomy and Physiology). Activity 2 is
also appropriate for an undergraduate freshman biology class.
PRIOR KNOWLEDGE
In order to get the most out of these activities, students should be familiar with the following terms and
concepts: the cell cycle and its regulation; genes and mutations; dominant and recessive genes.
BACKGROUND
Cancer consists of a group of diseases caused by mutations in the DNA of cells. Some mutations are
inherited, but most occur during a person’s lifetime as a result of random errors in replication.
Environmental factors that damage DNA, such as smoking and sunlight, can also cause mutations to
occur.
As a single cell in the body accumulates mutations, one of those mutations could provide a survival or a
growth advantage to the cell, causing the cell to divide at a faster-than-normal pace or to not die. The
resulting daughter cells with that mutation, which are dividing quickly, are more likely to accumulate
additional mutations. Additional mutations that affect cell division may cause those cells to divide even
faster. Eventually, a cell may acquire enough mutations that it starts to grow and divide uncontrollably
(Figure 2).
Figure 2. Schematic of cancer development. Cells accumulate mutations as they divide. Mutations that are most
advantageous for cell growth and survival are passed on to daughter cells, which, in turn, acquire further mutations and may
eventually become malignant cancer cells. (The arrows represent multiple cell divisions.)
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
Scientists have thus far identified about 140 different genes that, when mutated, can lead to the
development of cancer. Most cancers contain mutations in two to eight of these genes. The 140 or so
genes that drive the development of cancer fall into two categories that describe their effects on cell
division. One category consists of oncogenes, which are mutated genes whose protein products cause
cells to divide faster. The normal versions of oncogenes are called proto-oncogenes; they code for
proteins that stimulate normal growth and division. The second category consists of tumor suppressor
genes, which encode proteins that normally put the brakes on cell division and, when mutated, have
the effect of taking the brakes off.
Oncogenes and tumor suppressor genes affect several different cellular processes, which can be
grouped into cell growth and survival (genes involved in the cell cycle), cell fate (genes involved in
cellular differentiation), and genome maintenance (mostly DNA repair genes).
QUESTIONS AND DISCUSSION POINTS
Some possible discussion questions and answers follow.
1. Are cancer genes only present in people who have cancer?
The genes on the Cancer Patient Cards and Cancer Gene Cards are normal genes that are part of the
genomes of all people. People with cancer have mutations in subsets of these genes. When these genes
are mutated, they can contribute to cancer. The normal versions of the genes produce proteins that
have important functions in cells.
2. Does everyone who inherits a mutation in BRCA1 eventually get breast cancer?
The BRCA1 gene is a tumor suppressor gene, which means that both copies of the gene (or alleles) have
to be inactivated for cancer to develop. People who inherit a mutation in one allele have a much higher
risk of developing cancer, because they start with only one working copy of the gene in all their cells. If
an additional mutation occurs on the other allele in one cell, it may lead to cancer. The cancer cards
also show that patients with BRCA1 mutations may have other types of cancer (i.e., glioma or hepatic
cancer) than breast cancer. The type of cancer that develops depends on which cell type in the body
first gets two inactivating (or loss-of-function) mutations in the BRCA1 gene.
3. Do mutated tumor suppressor genes and oncogenes carry different types of mutations? As
explained in the answer above, tumor suppressor genes have to have two loss-of-function mutations
for cancer to develop. Oncogenes carry mutations that increase the activity of the gene and its gene
product to stimulate the growth and survival of cells. Because these are gain-of-function mutations, a
single mutation in one allele of the gene is sufficient to contribute to cancer.
4. In the video clip, some tumors had hundreds or even thousands of mutations. Why do these
cancer cards only list three to six mutations?
The cards only list the mutations that may cause a cancer to develop; these are so-called driver
mutations. Cancers often have additional mutations that occur as a cancer progresses, but these
mutations do not drive the disease. They are referred to as passenger mutations. Cancers with hundreds
of mutations mostly have passenger mutations (see Figure 3).
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
5. What is the difference between driver and passenger mutations? How do you know which is
which?
Mutations occur at random as a cell divides or as a result of environmental factors. Driver mutations
provide survival and growth advantages to a cell; cells with these mutations are more likely to divide
and survive, and the mutations are maintained in the population of cells in the final cancer.
A cell that acquires a driver mutation may also have some other mutations that do not provide a growth
advantage. Although there is no selection for these passenger mutations, these will be carried along as
a cell with driver mutations divides and multiplies. Passenger mutations will therefore also be present in
cells of the final cancer.
A key challenge for researchers is to distinguish driver from passenger mutations. By analyzing
thousands of cancer genomes, researchers can determine which genes are most frequently mutated in
different cancers and thus likely to be involved in cancer development.
6. How does smoking cause cancer? The chemicals in cigarettes (e.g., tar, arsenic, benzene) cause
mutations to occur. As more and more mutations accumulate in different cells, it is more likely that
some of these mutations will cause cancer.
7. Although cancer can strike at any age, why are older people more likely to have cancer?
Cancer becomes more likely as we age and as damage to our DNA builds up. Advancing age is a high
risk factor for cancer, with persons over 65 year of age accounting for 60 percent of newly diagnosed
malignancies and 70 percent of all cancer deaths (see Berger et al.).
Figure 3. Driver versus
passenger mutations in
cancer. A single fertilized egg
gives rise to the thousands of
cells in the body. In this figure,
we see the lineage of cell
division from a fertilized egg to
a single cell within a cancer.
Mutations may occur in a
normal cell as a result of cell
division and the effects of
environmental and lifestyle
factors, such as smoking or
sunlight. Once the first cancer-
causing, or driver, mutations
occur, defects in cellular
processes—for example, in
DNA repair—may cause more
mutations to occur.
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
OPTIONAL RESEARCH PROJECT
After completing either Activity 1 or Activity 2, ask students to research one or more of the genes on
their cancer card. Suggested websites for their research include the National Institutes of Health’s
(NIH’s) Genetics Home Reference website, the Online Mendelian Inheritance in Man (OMIM) online
catalog, the PubMed website, and the COSMIC database. Suggested questions for students to research
include:
• What is the normal function of the gene? (Include whether it is a proto-oncogene or tumor
suppressor gene.)
• Specifically, what does the mutated version of the gene do that contributes to cancer?
• In what other type(s) of cancer is the gene mutated?
• Are the mutations loss-of-function or gain-of-function types?
The product of this research extension project could be a scientific article, a miniposter, a pamphlet, or
a concept map, such as the example below.
TP53
Mutant Gene
Normal Gene
Is found in human cancers: lung, breast, colorectal, glioma (brain),
melanoma, hepatic (liver), pancreatic, and leukemia.
Tumor
Chromosome
Suppressor Cell Survival
17
Gene
54.56% of mutations are missense mutations, but other mutation types
can occur (i.e., nonsense, insertions, and deletions).
Produces a protein Keeps cells from
Is nicknamed the
called tumor protein growing and dividing
"Guardian of the
p53, which regulates too fast or
Genome."
cell division. uncontrollably.
Most mutations are recessive loss-of-function mutations and require both
copies of the TP53 gene to be mutant.
Can arrest the cell
cycle, trigger
apoptosis or
senescence, and
repair DNA.
Most mutations destroy the ability of the protein to bind to its target DNA.
The TP53 gene had the highest frequency of occurrence in the cancer card
activity completed in class. It occurred in 16 of the 32 cards.
www.BioInteractive.org Published August 2014; revised May 2016
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
RELATED BIOINTERACTIVE RESOURCES
1. Click and Learn: The Eukaryotic Cell Cycle and Cancer
This modular Click and Learn is adaptable to all levels of high school biology and introductory college
biology. It describes the cell cycle phases and checkpoints, protein regulators, their roles in cell cycle
progression, and how mutated versions of these proteins can lead to cancer.
2. Medicine in the Genomic Era, 2013 Holiday Lectures on Science Series, Lecture 2: Cancer as a
Genetic Disease, by Dr. Charles Sawyers
Dr. Sawyers presents an overview of cancer biology and describes how understanding the molecular
mechanisms involved in a type of cancer, chronic myeloid leukemia, resulted in the development of
Gleevec, one of the first targeted cancer drugs.
3. Medicine in the Genomic Era, 2013 Holiday Lectures on Science Series, Lecture 4: From Cancer
Genomics to Cancer Drugs, by Dr. Charles Sawyers
Cancers can now be classified not only by the type of tissue and cell that they affect, but also by the
genes that are mutated. As Dr. Charles Sawyers reveals in this lecture, both types of classification are
necessary for devising new targeted therapies.
4. Learning from Patients: The Science of Medicine, 2003 Holiday Lectures on Science Series, Lecture 1:
Research Mechanics: Putting the Brakes on Cancer, by Dr. Bert Vogelstein
Cancers are caused by an accumulation of mutations that alter the activity of genes involved in
controlling cell birth, growth, and death. Dr. Vogelstein explains that all cancers stem from alterations
that allow cell division to outstrip cell demise.
5. Learning from Patients: The Science of Medicine, 2003 Holiday Lectures on Science Series, Lecture 2:
Chaos to Cure: Bringing Basic Research to Patients, by Dr. Bert Vogelstein
The identification of hundreds of genes involved in the formation and spread of cancer is leading to
promising new methods for diagnosis, prevention, and treatment. Dr. Vogelstein reviews some of these
methods, including one that his own lab is working on.
6. Click and Learn: The p53 Gene and Cancer
In this Click and Learn activity, students learn what p53 does and how interfering with its function can
lead to cancer.
7. Animation: Angiogenesis
This animation illustrates what happens in a tumor, from cells dividing at an abnormally high rate, to the
recruitment of blood vessels, and finally metastasis.
8. Animation: VEGF (Vascular Endothelial Growth Factor)
This animation explains how cancers release VEGF to stimulate the growth of blood vessels and increase
blood supply, thus supporting their further growth.
9. Animation: Mismatch Repair
This animation shows how DNA polymerase’s proofreading system works during DNA replication.
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
10. Animation: Using p53 to Fight Cancer
This animation illustrates a new, experimental cancer treatment that takes advantage of the fact that
many cancer cells have a mutant and inactive form of the protein p53.
11. Animation: CML and Gleevec
Through this animation, students learn that chronic myeloid leukemia (CML) is caused by a mutation
that leads to an abnormal protein that is always active and stimulates cell growth. The drug Gleevec has
a shape that fits into the active site of the abnormal protein and stops its function.
12. Animation: Gleevec
This animation shows how the drug Gleevec has been designed to disrupt the growth of cancer cells by
blocking a binding site of an abnormal protein found only in tumor cells and not in normal cells.
13. Animation: Genetic Mutations and Disease
This poster for the 2013 Holiday Lectures on Science series, Medicine in the Genomic Era, illustrates the
difference between germline and somatic cell mutations.
14. Animation: The Evolution of Cancer
This article summarizes how cancers grow and spread by a process akin to evolution.
15. Animation: Understanding Cancer Diversity
In this article, students learn how cancer occurs when a cell acquires the ability to reproduce
aggressively and invade other tissues.
REFERENCES
Beer, Tomasz. “Cancer Clinical Trials of Tomorrow.” The Scientist. April 1, 2013. http://www.the-
scientist.com/?articles.view/articleNo/34761/title/Cancer-Clinical-Trials-of-Tomorrow/.
Berger, Nathan A., Panos Savvides, Siran M. Koroukian, Eva F. Kahana, Gary T. Deimling, Julia H. Rose,
Karen F. Bowman, and Robert H. Miller. “Cancer in the Elderly,” by invitation. Transactions of the
American Clinical and Climatological Association 117 (2006): 147–156.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1500929/.
Catalogue of Somatic Mutations in Cancer (COSMIC).
http://cancer.sanger.ac.uk/cancergenome/projects/census/.
Hanahan, Douglas, and Robert A. Weinberg. “The Hallmarks of Cancer.” Cell 144, no. 5 (March 4, 2011):
646–674. doi:10.1016/j.cell.2011.02.013.
HUGO Gene Nomenclature Committee (HGNC). http://www.genenames.org/cgi-bin/search.
Vogelstein, Bert, Nickolas Papadopoulos, Victor E. Velculescu, Shibin Zhou, Luis A. Diaz Jr., and Kenneth
W. Kinzler. “Cancer Genome Landscapes.” Science 339, no. 6127 (March 29, 2013): 1546–1558).
doi:10.1126/science.1235122.
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2013 Holiday Lectures on Science OVERVIEW OF CANCER DISCOVERY ACTIVITIES
Medicine in the Genomic Era EDUCATOR MATERIALS
SUGGESTED RUBRIC FOR 3-2-1 ANALYSIS
Below Expectations Meets Expectations Exceeds Expectations
Knowledge Items are missing or All items are complete. All items are complete.
incomplete. All items reflect original All items reflect original
Items do not reflect ideas. ideas and are of high
original ideas. Items reflect an quality.
Items do not reflect an understanding of the Items reflect a much
understanding of the concepts and learning deeper understanding and
concepts and learning objectives. application of the key
objectives. concepts and learning
objectives.
Thinking/Reasoning Items do not reflect Items reflect solid thinking Items reflect solid thinking
deeper thinking or further about the key concepts about the key concepts
application of the key and learning objectives. and learning objectives
concepts and learning and suggest applications
objectives. or questions beyond the
key concepts of the
activity.
Clarity/Presentation Submission was poorly Submission was clearly Submission was clearly
written and unclear. organized and well organized, well written,
written. and included additional
images, ideas, or
suggestions that went
beyond the assignment.
AUTHORS
These activities were written by Ann Brokaw, Rocky River High School, Rocky River, OH; Laura Bonetta, PhD, and Eriko Clements, PhD, HHMI.
The Cancer Patient Cards were developed by Travis Dittmer, PhD.
Edited by Laura Bonetta, PhD, HHMI, Robin Heyden, consultant, and Susan Dodge, consultant; copyedited by Barbara Resch and Linda Felaco.
Reviewed by Nancy Staub, PhD, Gonzaga University, WA, and David McDonald, PhD, North Carolina Central University.
FIELD TESTERS
Melissa Csikari, Helen Snodgrass, David Knuffke, Lisa Mueller, Laura Novillo, Robert O'Brien, Sarah Freilich, Sunita Meyers, Suzanne Sikes, Caitlin
Ullock, Beth Pethel, Robin Cochran Dirksen
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