Genetic Basis of Cancer Quiz
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Cancer is characterized by uncontrolled cell ______.

division

Most cancers originate from a single ______.

cell

Cancers can be categorized into benign and ______ types.

malignant

The process of cancer development is often referred to as a ______ process.

<p>multistep</p> Signup and view all the answers

Tumor ______ are viruses known to directly cause cancer.

<p>viruses</p> Signup and view all the answers

Examples of DNA viruses that may cause cancer include hepatitis B and ______.

<p>papillomavirus</p> Signup and view all the answers

Rous sarcoma virus (RSV) causes sarcomas in ______.

<p>chickens</p> Signup and view all the answers

Chemical ______ can contribute to cancer by damaging DNA.

<p>carcinogens</p> Signup and view all the answers

Epstein-Barr virus is a causative agent in ______ lymphoma.

<p>Burkitt</p> Signup and view all the answers

Approximately ______% of human cancers are not induced by viruses.

<p>80</p> Signup and view all the answers

Specific genes capable of inducing cell transformation are called ______.

<p>oncogenes</p> Signup and view all the answers

The first oncogene to be identified was the ______ gene of RSV.

<p>src</p> Signup and view all the answers

Mutations in proto-oncogenes are typically ______ in nature.

<p>dominant</p> Signup and view all the answers

The prototype tumor suppressor gene is ______.

<p>Rb</p> Signup and view all the answers

______ is required for apoptosis induced by DNA damage.

<p>p53</p> Signup and view all the answers

Tumor suppressor genes act to inhibit cell ______ and tumor development.

<p>proliferation</p> Signup and view all the answers

Rb inhibits progression past the restriction point in ______.

<p>G1</p> Signup and view all the answers

Cdk4, 6/cyclin D complexes promote passage through the restriction point by ______ and inactivating Rb.

<p>phosphorylating</p> Signup and view all the answers

The activity of Cdk4, 6/cyclin D is inhibited by ______.

<p>p16</p> Signup and view all the answers

Wild-type p53 is required for both cell cycle arrest and ______ induced by DNA damage.

<p>apoptosis</p> Signup and view all the answers

Cell cycle arrest is mediated by induction of the Cdk inhibitor ______.

<p>p21</p> Signup and view all the answers

Loss-of-function in a tumor-suppressor gene can allow ______ growth to occur.

<p>cancerous</p> Signup and view all the answers

Normal, nonmutated genes with the potential to become oncogenes are known as ______.

<p>proto-oncogenes</p> Signup and view all the answers

Missense mutations in ras genes are frequently found in a large number of different ______.

<p>cancers</p> Signup and view all the answers

Gains-of-function mutations generally increase the ______ of protein or alter its structure.

<p>amount</p> Signup and view all the answers

The ______ family members PUMA and Noxa are involved in the apoptosis pathway.

<p>Bcl-2</p> Signup and view all the answers

The first human tumor-suppressor gene identified was the ______ gene.

<p>retinoblastoma</p> Signup and view all the answers

Alfred Knudson proposed a 'two-hit' model for ______.

<p>retinoblastoma</p> Signup and view all the answers

About ______% of all human cancers are associated with defects in the p53 gene.

<p>50</p> Signup and view all the answers

The Rb protein regulates the transcription factor ______, which is essential for cell cycle progression.

<p>E2F</p> Signup and view all the answers

Apoptosis is facilitated by proteases known as ______.

<p>caspases</p> Signup and view all the answers

Tumor-suppressor genes prevent ______ growth.

<p>cancerous</p> Signup and view all the answers

The functions of tumor-suppressor genes include negatively regulating cell ______.

<p>division</p> Signup and view all the answers

The two forms of retinoblastoma are inherited and ______.

<p>non inherited</p> Signup and view all the answers

If there is no functional Rb protein, a cell can always progress through the ______ cycle.

<p>cell</p> Signup and view all the answers

P53 promotes pathways that activate genes for DNA ______.

<p>repair</p> Signup and view all the answers

The inhibition of E2F prevents the transcription of certain genes required for DNA replication and cell division, and the protein kinase ______ negatively regulates cyclin-dependent kinases.

<p>p16</p> Signup and view all the answers

The NF1 protein stimulates Ras to hydrolyze its GTP to ______.

<p>GDP</p> Signup and view all the answers

APC is a negative regulator of a cell-signaling pathway that leads to the activation of genes that promote ______.

<p>cell division</p> Signup and view all the answers

P53 acts as a checkpoint protein and positively regulates a few specific target genes while negatively regulating others, acting as a sensor of ______.

<p>DNA damage</p> Signup and view all the answers

BRCA1 and BRCA2 proteins are involved in the cellular defense against ______.

<p>DNA damage</p> Signup and view all the answers

Tumor-suppressor genes fall into two categories: those that negatively regulate cell division and those that maintain ______.

<p>genome integrity</p> Signup and view all the answers

Checkpoint proteins detect genetic abnormalities and prevent ______.

<p>cell division</p> Signup and view all the answers

Epigenetics is the study of heritable traits that happen without changes to the ______ sequence.

<p>DNA</p> Signup and view all the answers

Epigenetic changes can lead to functionally relevant alterations in the ______.

<p>genome</p> Signup and view all the answers

Examples of mechanisms that produce epigenetic changes include DNA ______ and histone modification.

<p>methylation</p> Signup and view all the answers

Epigenetic changes may directly contribute to disease ______.

<p>symptoms</p> Signup and view all the answers

One indirect association of epigenetic changes and disease suggests that a third factor may be involved, like a toxic ______.

<p>agent</p> Signup and view all the answers

Abnormal chromatin modifications in cancer cells include DNA methylation and histone ______.

<p>modification</p> Signup and view all the answers

Mutations in genes that encode chromatin-modifying proteins can lead to ______ effects on gene expression.

<p>widespread</p> Signup and view all the answers

Covalent modification of histones affects how genes are ______.

<p>expressed</p> Signup and view all the answers

Environmental agents can directly alter the functions of ______ proteins.

<p>chromatin-modifying</p> Signup and view all the answers

Tobacco smoke and charbroiled food contain polycyclic aromatic ______.

<p>hydrocarbons</p> Signup and view all the answers

A common type of mutation in cancer involves the gene encoding a DNA ______ enzyme.

<p>methyltransferase</p> Signup and view all the answers

Histone demethylases are involved in removing ______ groups from histones.

<p>methyl</p> Signup and view all the answers

Acute myeloid leukemia is associated with mutations in genes encoding DNA ______.

<p>methyltransferases</p> Signup and view all the answers

Endocrine disruptors are associated with cancer of the breast, prostate, and ______.

<p>thyroid</p> Signup and view all the answers

5-azacytidine and decitabine are examples of drugs that inhibit ______ to treat cancer.

<p>DNA methyltransferase</p> Signup and view all the answers

Flashcards

Cancer Definition

Cancer is a disease where cells divide uncontrollably, forming malignant tumors that can invade other tissues.

Cancer Origin

Most cancers begin from a single cell and grow clonal, meaning cells from a single original cell all share the same characteristics.

Cancer Stages

Cancers are classified as malignant (invasive into surrounding tissues) or metastatic (spread to distant sites).

Cancer Multistep Process

Cancer development is a process involving multiple genetic changes, often starting from a benign growth and progressing as more genetic mutations occur.

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Tumor Viruses

Certain viruses can cause cancer in animals, including humans.

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Carcinogen

Substances such as radiation and some chemicals that cause cancer by damaging DNA and causing mutations.

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Retroviruses

A family of viruses that are known to cause cancer.

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DNA Viruses

Another family of viruses that are associated with causing cancer in many species, including humans.

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Oncogenes

Genes capable of transforming normal cells into cancerous cells.

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Proto-oncogenes

Normal genes that can become oncogenes when mutated.

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Tumor Suppressor Genes

Genes that normally prevent tumor development.

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Rb gene

A prototype tumor suppressor gene linked to retinoblastoma.

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p53 gene

A tumor suppressor gene important for triggering programmed cell death (apoptosis).

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Cell Transformation

The process by which normal cells develop into cancerous cells.

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Mutations are typically dominant

One mutated copy of a proto-oncogene can cause cell transformation

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Epigenetics

Changes in gene expression that are not caused by alterations to the DNA sequence itself, but rather by modifications like DNA methylation or histone modifications.

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DNA methylation

The addition of a methyl group to a DNA base, typically cytosine. This can silence gene expression by preventing transcription factors from binding.

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Histone modification

Chemical changes to histone proteins, which package DNA. These modifications can alter how tightly DNA is wound, affecting gene accessibility and expression.

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Rb protein

Inhibits cell cycle progression by preventing cells from passing the G1 restriction point.

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p16

Inhibits Cdk4/6/cyclin D complexes, thus preventing cell cycle progression.

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Cdk4/6/cyclin D

Promote cell cycle progression by phosphorylating and inactivating Rb.

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p53

Mediates cell cycle arrest and apoptosis in response to DNA damage.

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p21

A Cdk inhibitor induced by p53, leading to cell cycle arrest.

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Ras protein

GTPase involved in cell signaling; mutation can lead to uncontrolled cell growth.

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Mutation in proto-oncogene

Change to a proto-oncogene that make it an oncogene.

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Missense Mutation

A type of point mutation that changes a single amino acid in a protein, potentially affecting its function.

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Gene Amplification

An increase in the number of copies of a specific gene within a cell, leading to an overproduction of the gene's product.

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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 insertion of viral DNA into a host cell's genome.

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Apoptosis

Programmed cell death, a process where cells are systematically dismantled and eliminated.

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Caspases

A family of proteases that play a key role in executing apoptosis by breaking down the cell's components.

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E2F Inhibition

The process of blocking E2F, a transcription factor, from activating genes necessary for DNA replication and cell division.

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p16 Role

The protein kinase p16 acts as a brake on the cell cycle, preventing the transition from the G1 phase to the S phase by negatively regulating cyclin-dependent kinases.

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NF1 Function

The NF1 protein regulates the activity of Ras, a signaling protein that promotes cell division. NF1 stimulates Ras to deactivate itself.

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APC Role

APC is a protein that negatively regulates a signaling pathway involved in cell division, preventing the activation of genes that promote cell growth.

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Genome Integrity Maintenance

The cellular mechanisms that prevent mutations from occurring or eliminate mutant cells, ensuring the stability of the genetic code.

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p53 Function

A checkpoint protein that acts as a sensor of DNA damage, triggering a cascade of responses to repair damaged DNA or eliminate damaged cells.

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BRCA1 and BRCA2

Proteins involved in DNA repair, protecting the cell from accumulating mutations. They can also trigger apoptosis (programmed cell death) if damage cannot be repaired.

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Epigenetics Definition

The study of inherited traits that are not encoded in the DNA sequence, but are influenced by factors that modify gene expression.

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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 classified by the cell type that becomes cancerous; over 100 types have been identified
  • Most cancers originate from a single cell; a characteristic known as clonal in origin. Cancer cells divide to produce more cancer cells
  • Cancer is a multistep process; beginning as a benign, non-invasive growth. More genetic changes cause cancerous growth

Characteristics of Cancer

  • Most cancers originate from a single cell, a clonal origin
  • Cancer is a multistep process beginning as a benign, non-invasive growth
  • Additional genetic changes cause cancerous growth
  • Cancer may be staged as malignant (invasive, invades surrounding tissues) or metastatic (moves to a different site in the body)

Causes of Cancer

  • Radiation and many chemical carcinogens damage DNA and induce mutations
  • Other chemical carcinogens contribute to cancer development by stimulating cell proliferation
  • Viruses cause cancer in humans and other species

Tumor Viruses

  • Several families of animal viruses, known as tumor viruses, are capable of causing cancer in experimental animals and humans
  • Different virus families have different human tumor types, different genome sizes
  • The majority of human cancers (about 80%) are not induced by viruses; they are caused by other factors

Cancer Results From Alterations in Genes

  • Cancer results from alterations in critical regulatory genes that control cell proliferation, differentiation, and survival

Oncogenes

  • Specific genes (oncogenes) are capable of inducing cell transformation, providing insights into the molecular basis of cancer
  • The identification of viral oncogenes led to the identification of cellular oncogenes involved in non-virus-induced cancers
  • The connection between viral and cellular oncogenes was shown in studies of highly oncogenic retroviruses.
  • One of the first oncogenes discovered was the src gene of Rous sarcoma virus(RSV). Further studies identified more than 2 dozen oncogenes in various retroviruses.
  • Proto-oncogenes are normal genes but can become oncogenes when mutated; mutations in proto-oncogenes are typically dominant
  • Oncogenes are abnormally expressed or mutated forms of the related proto-oncogenes

Tumor Suppressor Genes

  • Tumor suppressor genes normally inhibit cell growth and development
  • The prototype tumor suppressor gene Rb was identified through studies of retinoblastoma inheritance.
  • Loss or mutational inactivation of Rb and other tumor suppressor genes (like p53) contributes to the variety of human cancers
  • Rb proteins inhibit the cell cycle by not allowing passage from G1 to S
  • p53 is needed for apoptosis after DNA damage to initiate programmed cell death. p53 promotes DNA repair and cell division arrest, and activates genes regulating apoptosis as needed.

Apoptosis

  • Apoptosis is a programmed cell death characterized by cell shrinkage and chromatin condensation
  • Apoptosis is facilitated by proteases called caspases that degrade cell components
  • Cells in apoptosis eventually break down into vesicles and are phagocytized(eaten) by immune cells

Mutations in Proto-oncogenes

  • Four types of mutations that can change proto-oncogenes to oncogenes are missense mutation, gene amplification, chromosomal translocation, and viral integration.

Rb Protein Regulates Cell Division

  • More recent research has detailed how the Rb protein halts the proliferation of cancer cells by regulation of E2F transcription factor
  • Binding of Rb to E2F blocks the protein's activity, preventing the progression from G1 phase to S
  • Absence of functional Rb protein allows uncontrolled cell division

p53

  • The p53 gene is a crucial tumor suppressor gene
  • p53 acts as a checkpoint, determining if a damaged cell can repair before division
  • Fifty% of human cancers are related to p53 gene defects
  • p53 regulates repair mechanisms, arrests cell division, and activates genes that induce apoptosis (programmed cell death)

Epigenetics

  • Epigenetics involves heritable traits that don't change DNA sequences
  • Epigenetic mechanisms alter gene expression without altering the underlying DNA sequence
  • Epigenetic factors can contribute to cancer by changes in DNA methylation and histone modifications

Environmental Agents and Cancer

  • Some environmental agents alter chromatin-modifying proteins impacting gene expression.
  • Associations between specific agents and types of cancer are noted, but further study may be needed.
  • Several examples of environmental agents are provided

Cancer Treatments

  • Researchers are investigating drugs that affect DNA methylation and inhibit abnormal cell proliferation.

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Test your knowledge on the genetic foundations of cancer and its characteristics. This quiz covers the multistep process of cancer development, the origin of cancer cells, and various causes of cancer. Challenge yourself to learn more about this complex disease and its implications.

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