Genetic Basis of Cancer

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Questions and Answers

What is the primary characteristic of cancer?

  • Stable cell mutation rates
  • Controlled cell division
  • Uncontrolled cell division (correct)
  • Uniform cell structure

How many kinds of human cancers have been identified?

  • More than 100 (correct)
  • Fewer than 10
  • More than 50
  • Exactly 100

What does it mean for most cancers to be of clonal origin?

  • They originate from multiple cells
  • They are always benign
  • They originate from a single cell (correct)
  • They are caused by external factors

Which statement best describes the multistep process of cancer?

<p>A benign growth can evolve into cancerous growth with genetic changes (D)</p> Signup and view all the answers

Which of the following is NOT a way chemicals contribute to cancer development?

<p>Stimulating beneficial cell proliferation (B)</p> Signup and view all the answers

Which virus is known to cause cervical cancer in humans?

<p>Papillomavirus (C)</p> Signup and view all the answers

What type of cancer is associated with Rous sarcoma virus (RSV)?

<p>Sarcomas (B)</p> Signup and view all the answers

Which characteristic defines a malignant cancer?

<p>It invades surrounding tissue (D)</p> Signup and view all the answers

What is the primary type of individual that Burkitt lymphoma occurs in?

<p>Individuals with a weakened immune system (A)</p> Signup and view all the answers

What percentage of human cancers are estimated to arise from causes other than viruses?

<p>80% (B)</p> Signup and view all the answers

Which of the following genes is identified as a prototype tumor suppressor gene?

<p>Rb gene (C)</p> Signup and view all the answers

What role do mutations in proto-oncogenes typically play in cancer development?

<p>They cause normal cells to become cancerous. (D)</p> Signup and view all the answers

Which protein is required for apoptosis induced by DNA damage?

<p>p53 (C)</p> Signup and view all the answers

What is a characteristic of tumor suppressor genes compared to oncogenes?

<p>They inhibit tumor development. (A)</p> Signup and view all the answers

What is the relationship between oncogenes and proto-oncogenes?

<p>Oncogenes are mutated or abnormally expressed proto-oncogenes. (D)</p> Signup and view all the answers

Which oncogene was the first to be identified from a retrovirus?

<p>Src (D)</p> Signup and view all the answers

What role does Rb play in the cell cycle?

<p>Inhibits progression past the restriction point (B)</p> Signup and view all the answers

Which protein inhibits Cdk4,6/cyclin D complexes?

<p>p16 (C)</p> Signup and view all the answers

What type of mutation results in the activation of an oncogene?

<p>Gain-of-function mutation (B)</p> Signup and view all the answers

Which of the following is NOT classified as a tumor suppressor gene?

<p>Cdk4 (C)</p> Signup and view all the answers

What is the primary function of wild-type p53 in response to DNA damage?

<p>Mediates cell cycle arrest and apoptosis (C)</p> Signup and view all the answers

Which characteristic is typical of proto-oncogenes?

<p>Nonmutated genes with the potential for mutation (D)</p> Signup and view all the answers

Which of the following mutations is associated with the Ras protein acting as an oncogene?

<p>Decreased GTP hydrolysis (A)</p> Signup and view all the answers

What is the effect of oncogenes on cellular behavior?

<p>They lead to uncontrolled cell proliferation (D)</p> Signup and view all the answers

In the context of tumor suppressors, what does 'loss-of-function' refer to?

<p>The gene's protein product is inactive or absent (A)</p> Signup and view all the answers

Which protein is a transcription factor that can become an oncogene?

<p>myc (D)</p> Signup and view all the answers

What is the primary function of the NF1 protein in cell division?

<p>To enhance GTP hydrolysis, reducing Ras activity. (D)</p> Signup and view all the answers

How does the APC protein affect cell division?

<p>It negatively regulates a pathway that promotes cell division. (B)</p> Signup and view all the answers

What function does p53 serve in cellular processes?

<p>It is a transcription factor that regulates genes involved in cell cycle checkpoint and apoptosis. (D)</p> Signup and view all the answers

What is the primary function of BRCA1 and BRCA2 proteins?

<p>To facilitate DNA repair and promote apoptosis when repair fails. (C)</p> Signup and view all the answers

What characterizes tumor-suppressor genes?

<p>They may function through mechanisms that ensure genome integrity. (D)</p> Signup and view all the answers

What is the focus of epigenetics in cellular biology?

<p>Heritable traits that occur without altering the DNA sequence. (A)</p> Signup and view all the answers

Which of these describes the role of checkpoint proteins?

<p>To detect genetic abnormalities and regulate cell division. (D)</p> Signup and view all the answers

What is the primary role of the p53 protein in relation to DNA damage?

<p>To activate genes that promote DNA repair and apoptosis. (A)</p> Signup and view all the answers

In the context of retinoblastoma, what does the 'two-hit' model imply?

<p>Individuals with the inherited form require only one additional mutation. (D)</p> Signup and view all the answers

What effect does the Rb protein have on the transcription factor E2F?

<p>It inhibits E2F to prevent cell cycle progression. (B)</p> Signup and view all the answers

What type of retinoblastoma typically occurs in the late stages of life?

<p>Non-inherited retinoblastoma. (A)</p> Signup and view all the answers

Which of the following accurately describes the process of apoptosis?

<p>It is a programmed cell death process resulting in cell shrinkage. (D)</p> Signup and view all the answers

What typically happens when tumor-suppressor genes like Rb or p53 lose their function?

<p>There is an increased risk of cancer development. (A)</p> Signup and view all the answers

Caspases are associated with which cellular process?

<p>Programmed cell death (apoptosis). (D)</p> Signup and view all the answers

Which gene was the first human tumor-suppressor gene identified?

<p>Retinoblastoma (Rb) gene. (A)</p> Signup and view all the answers

How does the loss of p53 gene function affect cancer progression?

<p>It prevents apoptosis and promotes tumor growth. (C)</p> Signup and view all the answers

Which of the following best describes how tumor-suppressor genes function?

<p>They inhibit processes that would lead to cancerous growth. (A)</p> Signup and view all the answers

Which mechanisms can alter gene expression without changing the DNA sequence?

<p>DNA methylation and histone modification (D)</p> Signup and view all the answers

How can epigenetic changes indirectly contribute to disease?

<p>A third factor may be involved. (A)</p> Signup and view all the answers

What type of chromatin modification is commonly abnormal in cancer cells?

<p>DNA methylation (D)</p> Signup and view all the answers

What can result from mutations in genes encoding chromatin-modifying proteins?

<p>Widespread effects on gene expression (A)</p> Signup and view all the answers

Which cancer is associated with mutations in DNA methyltransferase?

<p>Leukemia (A)</p> Signup and view all the answers

What is a common environmental agent associated with lung cancer?

<p>Polycyclic aromatic hydrocarbons (A)</p> Signup and view all the answers

Which environmental agent is linked to multiple myeloma and lymphoma?

<p>Benzene (A)</p> Signup and view all the answers

Which modification is made by histone acetyltransferase?

<p>Attachment of acetyl groups to histones (A)</p> Signup and view all the answers

What is a key feature of epigenetic changes caused by environmental agents?

<p>They may result in both cancer and genetic changes. (C)</p> Signup and view all the answers

Which type of histone modification is linked to breast cancer?

<p>Histone modification by acetylation (D)</p> Signup and view all the answers

Which treatment is being explored to target epigenetic changes in cancer?

<p>Inhibition of DNA methylation with decitabine (A)</p> Signup and view all the answers

What is a potential outcome of chromatin remodeling in cancer cells?

<p>Altered positions of histones (C)</p> Signup and view all the answers

Which cancer type is NOT commonly associated with mutations in histone methyltransferase?

<p>Non-small cell lung cancer (C)</p> Signup and view all the answers

Flashcards

Cancer Definition

Uncontrolled cell division resulting in a genetic disease at the cellular level.

Cancer Origin

Most cancers begin from a single cell, making a clonal growth.

Cancer Process

A multi-step process, starting as a benign growth and becoming malignant through genetic changes.

Cancer Stages

Cancers can be staged based on invasiveness. Malignant is invasive; metastatic spreads to other locations.

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Cancer Causes (Radiation)

Radiation damages DNA, causing mutations.

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Cancer Causes (Carcinogens)

Chemical carcinogens damage DNA, and also promote cell division.

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Tumor Viruses

Certain viruses, such as retroviruses and DNA viruses, can directly contribute to cancer development.

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Cancer Classifications

Cancers are categorized according to the type of cell affected; over a hundred types exist.

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Oncogenes

Genes that cause normal cells to turn cancerous when mutated.

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Proto-oncogenes

Normal genes that, when mutated, become oncogenes.

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Tumor Suppressor Genes

Genes that normally prevent tumour development.

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Rb gene

A key tumor suppressor gene, often mutated in cancers.

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p53 gene

A crucial tumor suppressor gene that regulates cell cycle and apoptosis.

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Cell Transformation

The process by which a normal cell becomes cancerous.

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Retroviruses

Viruses that can carry oncogenes.

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Viral Oncogenes

Oncogenes found in viruses that can cause cancer.

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Rb protein function

Rb inhibits cell cycle progression past the restriction point in G1.

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Cdk4/6-cyclin D complex

Phosphorylates and inactivates Rb, promoting cell cycle progression.

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p16 function

Inhibits Cdk4/6-cyclin D complexes, slowing cell cycle progression.

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p53 function

Crucial for cell cycle arrest and apoptosis in response to DNA damage.

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Ras protein

GTPase involved in cellular signaling; can become oncogenic with mutations.

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Gain-of-function mutation

A mutation that causes a protein to become overactive or to be expressed in an inappropriate place.

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Mutations triggering oncogenesis

Changes that can transform proto-oncogenes into oncogenes, often increasing protein levels, altering structure, or causing incorrect expression.

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E2F Inhibition

E2F is a protein that promotes gene transcription required for DNA replication and cell division. When E2F is inhibited, these genes are not expressed, preventing the cell cycle from progressing.

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p16 Role

p16 is a protein kinase that negatively regulates cyclin-dependent kinases (CDKs). This regulation prevents the cell from transitioning from the G1 phase to the S phase, thus halting cell division.

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APC Role

APC (Anaphase Promoting Complex) acts as a negative regulator of a signaling pathway that activates genes promoting cell division. By blocking this pathway, APC prevents uncontrolled cell growth.

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BRCA1 & BRCA2 Role

BRCA1 and BRCA2 are proteins involved in DNA repair and controlling cell division. They detect damage and attempt to repair it. If repair fails, they induce apoptosis.

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Genome Integrity

The ability of a cell to maintain the integrity of its DNA, through mechanisms that prevent mutations and remove damaged cells.

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Epigenetics

Changes in gene expression without altering the DNA sequence.

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Epigenetic Mechanisms

Processes that alter gene expression without changing the DNA sequence. Examples include DNA methylation and histone modification.

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DNA Methylation

Adding a methyl group to DNA, often silencing gene expression.

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Histone Modification

Altering histones (proteins DNA wraps around) to control access to genes.

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Epigenetics and Disease

Epigenetic changes can contribute to disease in different ways, either directly, as a consequence of disease, or indirectly due to a third factor.

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Cancer and Epigenetics

Abnormal epigenetic changes are common in cancer cells, affecting DNA methylation, histone modifications, and chromatin remodeling.

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Mutations in Chromatin-Modifying Proteins

Mutations in genes encoding proteins that regulate chromatin structure can disrupt normal gene expression.

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Environmental Agents and Epigenetics

Certain environmental factors can alter chromatin-modifying proteins, potentially contributing to cancer development.

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5-azacytidine and Decitabine

Drugs that inhibit DNA methyltransferase, potentially useful in cancer treatment.

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Epigenetic Changes in Cancer (Direct)

Epigenetic alterations directly contribute to cancer development.

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Epigenetic Changes in Cancer (Consequence)

Disease symptoms can cause epigenetic changes.

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Epigenetic Changes in Cancer (Indirect)

Epigenetic changes may occur indirectly due to a third factor, such as a toxic agent.

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Examples of Environmental Agents

Examples include polycyclic aromatic hydrocarbons, benzene, endocrine disruptors, cadmium, nickel, and arsenic.

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Epigenetics and Cancer Treatment

Researchers are developing drugs targeting epigenetic changes to treat cancer.

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Missense mutation

A type of point mutation that changes a single nucleotide in DNA, resulting in a codon that codes for a different amino acid.

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Gene amplification

An increase in the number of copies of a specific gene within a cell's genome.

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Chromosomal translocation

A genetic rearrangement where a piece of one chromosome breaks off and attaches to another chromosome.

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Viral integration

The process where a virus inserts its genetic material into the host cell's genome.

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What is the 'two-hit' model?

This model explains how two mutations in a tumor suppressor gene are needed for cancer to develop. The first mutation is inherited, while the second occurs during the individual's lifetime.

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How does Rb protein regulate cell division?

The Rb protein binds to a transcription factor called E2F, preventing it from activating genes needed for cell cycle progression.

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What is the role of p53 in DNA damage?

The p53 protein detects DNA damage and activates different pathways: DNA repair, cell cycle arrest, and apoptosis.

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What is apoptosis?

A programmed cell death process where a cell self-destructs in a controlled manner.

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What is the function of caspases?

Caspases are proteases that execute the breakdown of the cell during apoptosis.

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Study Notes

Genetic Basis of Cancer

  • Cancer is a disease of uncontrolled cell division, a genetic disease at the cellular level.
  • Human cancers are categorized by the cell type that becomes cancerous; more than 100 types have been identified.
  • Most cancers arise from a single cell, a clonal growth.
  • Cancer development is a multistep process, starting as a benign, non-invasive growth, then progressing with genetic changes to become cancerous.
  • Cancer can be staged based on its invasiveness; malignant is invasive, and metastatic spreads to a different body site.

Characteristics of Cancer

  • Most cancers originate from a single cell with clonal growth.
  • Cancer cells divide repeatedly forming a growth.
  • Cancer begins as a benign growth, not invasive.
  • Cancer's multi-step process involves additional genetic changes leading to cancerous growth.
  • Cancers are staged based on:
    • Malignant, meaning invasive, and spreading to surrounding tissues
    • Metastatic, meaning spread to different sites in the body.

Causes of Cancer

  • Radiation and many chemical carcinogens cause damage to DNA, leading to mutations.
  • Other chemical carcinogens stimulate cell proliferation, contributing to cancer development.
  • Viruses can cause cancer in humans and other species.
  • Members of several families of tumor viruses directly cause cancer in both experimental animals and humans.

Tumor Viruses

  • Specific virus families cause specific types of human cancers:
  • DNA viruses: Hepatitis B viruses, SV40 and polyomaviruses, Papillomaviruses, Adenoviruses, Herpesviruses
  • RNA viruses: Hepatitis C virus, Retroviruses

Oncogenes

  • Specific genes called oncogenes cause cell transformation, providing insights into cancer's molecular basis.
  • Studies of viral oncogenes led to the discovery of cellular oncogenes, involved in non-virus-induced cancers.
  • The key link between viral and cellular oncogenes was identified through retroviruses.
  • The first oncogene identified was the src gene of Rouse sarcoma virus. -Further studies have identified more than two dozen distinct oncogenes in various retroviruses.
  • Proto-oncogenes are normal genes that can mutate into oncogenes, causing cancer. -Mutations in proto-oncogenes are typically dominant, where a mutated gene product promotes cancer. -Oncogenes are mutated forms of proto-oncogenes, that are either overexpressed or are mutated in structure, resulting in the promotion of cancer.

Tumor Suppressor Genes

  • Tumor suppressor genes are involved in controlling cell growth, acting to inhibit proliferation and tumor development.
  • The Rb gene, a prototypical tumor suppressor gene is identified by studies of retinoblastoma inheritance patterns.
    • Loss or inactivation of Rb and other tumor suppressors, including p53, lead to numerous human cancers.
  • Tumor suppressor proteins act as inhibitors of cell proliferation and cell survival. -Rb, INK4, p53 proteins negatively regulate cell cycle progression. -p53 is essential in apoptosis, induced by DNA damage or other stimuli. Inactivation enhances tumor cell survival.

Rb Protein

  • Rb protein controls cell division, regulating the transcription factor E2F. -Phosphorylation of Rb by cyclin-dependent kinases causes detachment from E2F. This allows E2F and therefore activating cell cycle genes. -Binding of Rb to E2F inhibits its function, and prevents the cell from progressing through the cell cycle. -In the absence of a functional Rb protein, cells can progress through the cell cycle continually.

p53

  • p53 is a tumor suppressor gene involved in determining cell damage.
  • If DNA damage is detected, p53 promotes cellular pathways, activating DNA repair, halting cell division, and inducing apoptosis (programmed cell death).
  • About 50% of human cancers are connected with p53 gene defects.

Apoptosis

  • Apoptosis is a process of programmed cell death, involving cell shrinkage, chromatin condensation, and DNA degradation.
  • Caspases are proteases in apoptosis that act like "executioners".
  • In apoptosis, the cell breaks down into vesicles, and the immune system eventually removes them.

Epigenetics

  • Epigenetics is the study of heritable changes in gene expression that occur without changes to the underlying DNA sequence.
  • Epigenetic mechanisms such as DNA methylation and histone modifications alter gene expression without changing the DNA sequence.
  • Epigenetic factors are also linked to cancer.

Epigenetic Changes in Cancer

  • Several chromatin modifications, DNA methylation, histone modification, chromatin remodeling are abnormal in cancer cells.
  • Mutations in genes encoding chromatin-modifying proteins can cause inhibition, or increased function, influencing gene expression patterns.
  • Environmental agents can alter chromatin modifying protein functions.

Environmental Agents that Alter Chromatin Modifying Proteins

  • Some environmental agents directly alter chromatin-modifying protein functions.
  • Scientists are still investigating whether epigenetic changes from environmental agents cause cancer.
  • Various examples of environmental agents associated with cancer and epigenetic changes are listed in a table.

Cancer Treatments Aimed at Epigenetic Changes

  • Researchers are researching drugs to affect DNA methylation and covalent histone modifications, to inhibit cancer cells.
  • 5-azacytidine and decitabine are DNA methyltransferase inhibitors and are effective in diseases such as leukemia. However, mechanisms aren't entirely understood.

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