Cancer Mutation and Heterogeneity Overview

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Questions and Answers

What is a key characteristic of oncogenes?

They inhibit cell division.

They stimulate cell division. (correct)

They block differentiation.

They promote apoptosis.

What process must occur for a mutation to be passed on to daughter cells?

DNA replication only.

Clonal expansion of the cell. (correct)

Tumor suppressor activation.

Mutation must be repaired.

Which of the following best describes the effect of tumor heterogeneity on therapy?

It makes therapies more effective.

It leads to uniform cell response.

It prevents any form of mutation.

It complicates treatment approaches. (correct)

Which of the following mutations is associated with disruption of apoptosis?

P53 mutation. Signup and view all the answers

What is the result of the feedback loop in tumor biology?

Heightened opportunity for mutation and instability. Signup and view all the answers

What effect does DNA methylation have on gene expression?

It silences tissue-specific genes. Signup and view all the answers

Which of the following best describes histone acetylation?

It promotes an open chromatin structure. Signup and view all the answers

Which statement is true regarding cancer cell behavior?

Cancer cells reproduce and invade other tissues without restraint. Signup and view all the answers

What role do HDAC inhibitors play in cancer therapy?

They can increase transcription and induce cell cycle arrest. Signup and view all the answers

How do genetic mutations contribute to cancer progression?

They are often unresponsive to DNA repair mechanisms. Signup and view all the answers

What is the significance of epigenetic alterations in relation to cancer?

They can lead to dysregulated gene expression. Signup and view all the answers

What are the stages of tumor development?

Initiation, promotion, progression, invasion, and metastasis. Signup and view all the answers

Which statement accurately describes proto-oncogenes?

They typically promote cell growth and division. Signup and view all the answers

What is the primary function of tumor-suppressor genes?

Inhibiting cell division in response to DNA damage Signup and view all the answers

How do proto-oncogenes contribute to cancer development?

They gain function mutations, leading to increased cell division Signup and view all the answers

What is the significance of epigenetic changes in cancer?

They disrupt gene expression patterns affecting cell behavior Signup and view all the answers

Which statement about genetic mutations in cancer is accurate?

Mutations can affect both proto-oncogenes and tumor-suppressor genes. Signup and view all the answers

What does gene expression profiling assist with in cancer treatment?

Defining cancer subtypes based on patterns of gene activity Signup and view all the answers

Study Notes

Mutation and Tumour Heterogeneity

Mutations are random and occur in any cell at any time
Mutations are most likely to occur during DNA replication
Mutations are passed on only if the cell divides
Stepwise mutations lead to heterogeneity between tumors and within a single tumor
Heterogeneity has implications for cancer therapy

Tumor Co-option of Cellular Pathways

Tumors co-opt existing cellular pathways
Examples include disruption of:
- VEGF affecting angiogenesis
- P53 affecting apoptosis
- MAPK signaling affecting tissue invasion, growth, and proliferation

Selective Pressures

Tumors face selective pressures from the immune system, tumor suppressor genes, and the microenvironment.
These pressures can lead to tumor evolution and resistance to therapies.

Feedback Loop

Reduced tumor cell death leads to an increase in proliferation and DNA replication.
Increased DNA replication results in a greater chance of mutations and instability.

Oncogenes and Tumor Suppressor Genes

Oncogenes "push the accelerator" of cell growth, while tumor suppressor genes "release the brakes".

Oncogenes

Proto-oncogenes are typically one of:
- Cell division stimulators
- Differentiation blockers
- Apoptosis inhibitors
- Components of signaling pathways
- Growth factors.

Epigenetic Regulation of Gene Expression

Epigenetic alterations do not involve changes in the DNA sequence but impact gene expression.
DNA methylation:
- Addition of a methyl group to cytosine at CpG islands.
- Inhibits transcription by preventing promoter access.
- Plays a role in silencing tissue-specific genes.
Histone modifications:
- Acetylation is associated with euchromatin (active transcription).
- Deacetylation is associated with heterochromatin (inactive transcription).
Histone acetyltransferases, HDACs, and other proteins regulate these modifications.
Some cancer cells overexpress or aberrantly recruit HDACs leading to:
- Hypoacetylation
- Condensed chromatin structure
- Reduced transcription
HDAC inhibitors are cancer therapeutics that can increase transcription, leading to cell cycle arrest and apoptosis.

Regulation of Gene Expression

Cancer cells reproduce without restraint and invade foreign tissue
Most cancers originate from a single abnormal cell due to epigenetic or genetic changes.
A single mutation is not enough to cause cancer.
DNA repair mechanisms and redundancy prevent some mutations from causing damage.
There are multiple stages of development from mildly aberrant cells to cancer.

Multiple Stages of Tumor Development

Initiation
Promotion
Progression
Invasion
Metastasis

Gene Expression and Cancer

Cancer is a disease of dysregulated gene expression that grants a survival advantage to the cell.
Cancer growth relies on defective control of cell death and differentiation.

Gene Expression in Cancer Cells

Alterations in gene expression occur at all levels, including:
- Histone acetylation
- Activation of transcription factors
- Increased mRNA stability
- Increased translational control
- Protein modification

Loss of Cell Growth and Death Control

Proto-oncogenes stimulate cell growth and division in normal cells but become oncogenes in cancer (gain of function mutation).
Tumor suppressor genes inhibit cell division in response to DNA damage and allow repair to occur, but they lose function in cancer (loss-of-function).
Changes in gene expression have different effects.

Epithelial-Mesenchymal Transition (EMT)

The process by which epithelial cells lose polarity, cell-cell adhesion, and gain migratory and invasive properties.
Involved in natural processes like tissue repair, but also important for metastasis in cancer.

Gene Expression Profiling in Cancer

Gene expression profiling captures total gene activities across a genome enabling the definition of different subtypes of cancer.
Applications:
- Treatment selection by targeting specific deregulated pathways.
- Predicting cancer prognosis.
- Understanding mechanisms behind cancer development.

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Description

Explore the complex interactions of mutations and tumor heterogeneity in cancer. This quiz covers the mechanisms behind mutations, tumor co-option of cellular pathways, and the selective pressures that influence tumor evolution. Understand how these factors impact cancer therapy and treatment resistance.