Cancer Discovery: Classifying Cancer Genes

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 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.

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:
1. Cell growth and survival (genes involved in the cell cycle).
2. Cell fate (genes involved in cellular differentiation).
3. Genome maintenance (mostly DNA repair genes).

Questions:

1. What is the difference between Oncogenes and Proto oncogenes?

Use the information in the text above and the following video:
https://www.youtube.com/watch?v=cSXFjUpACWE
Oncogenes are mutated genes that have protein products that cause cells to divide
faster. Proto-oncogenes are the normal versions of oncogenes, those proto-
oncogenes code for proteins that rouse normal growth and division.

2. What is the difference between Proto-oncogenes and tumor suppressor

genes?
Use the information in the text above and the following video:
https://www.youtube.com/watch?v=cSXFjUpACWE
In contrast, proto-oncogenes lead to tumors by being activated, whereas tumor
suppressor genes lead to cancer when turned off.

3. Is p53 a tumor suppressor gene/oncogene? Explain the role of this gene in

causing cancer.
Use the information in the following video:
https://www.youtube.com/watch?v=cSXFjUpACWE
A tumor suppressor protein, p53 regulates cell division by preventing cells from
growing and dividing (proliferating) too rapidly or uncontrollably.

4. Consider genome maintenance genes:

a. Does DNA polymerase make mistakes during DNA replication?
b. How often?
c. Explain the proofreading system.
d. Explain what happens if a mutation occurs in the genes that encode
proofreading enzymes.
Use the information in the article below:
https://www.khanacademy.org/science/biology/dna-as-the-genetic-material/dna-
replication/a/dna-proofreading-and-repair#:~:text=DNA%20polymerases%20are%20the
%20enzymes,This%20process%20is%20called%20proofreading.

a. Yes, DNA polymerase makes mistakes during DNA replication.

b. This answer is based on information from a trusted governmental website because the
suggested article doesn’t mention anything about how often; it only says a few without any
specifications. Answer: It is estimated that replicative eukaryotic DNA polymerases make
errors approximately once every 104 – 105 nucleotides polymerized. Thus, each time a diploid
mammalian cell replicates, at least 100,000 and up to 1,000,000 polymerase errors occur.
(Preston et al., 2010)
c. Proofreading occurs when DNA polymerase checks its work for any errors to fix during DNA
synthesis.
d. According to information from the website, in many cases, mutations in genes that encode
proofreading and repair proteins are associated with heredity cancers (cancers that run-in
families). For example, Hereditary nonpolyposis colorectal cancer and xeroderma
pigmentosum which is a type of skin cancer