Patho: Neoplasia II (trans)

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Questions and Answers

What is the primary role of proto-oncogenes in normal cells?

To inhibit cellular growth

To repair DNA damage

To promote growth and regulation (correct)

To enhance apoptosis mechanisms

Which of the following transformations can activate proto-oncogenes?

Telomerase activation

Chromosomal inversions

Gene deletions

Point mutations (correct)

What is the Philadelphia Chromosome associated with?

Ovarian cancer

Chronic Myelogenous Leukemia (correct)

Lung cancer

Breast cancer

What type of chromosomal alteration is primarily linked to leukemias and lymphomas?

Chromosomal translocations Signup and view all the answers

What does the BCR in the Philadelphia Chromosome refer to?

Breakpoint cluster region Signup and view all the answers

What oncogenic change occurs due to the mutant protein produced by the BCR-ABL fusion?

Enhanced tyrosine kinase activity Signup and view all the answers

Which type of gene amplification involves the duplication of genes?

Gene duplication Signup and view all the answers

What happens when a mutant p53 monomer associates with a wild-type monomer?

The wild-type monomer is forced into a different conformation, blocking its binding ability. Signup and view all the answers

What is the t(8:14) translocation primarily associated with?

Burkitt’s Lymphoma Signup and view all the answers

What is a consequence of mutant p53 tetramers forming?

They inhibit specific DNA binding by preventing access to consensus sequences. Signup and view all the answers

Which characteristic is typical of neoplasms related to karyotypic abnormalities?

Heightened frequency of chromosomal abnormalities Signup and view all the answers

In tumors with one mutated TP53 allele, what typically occurs with the second allele?

The second allele remains wild-type. Signup and view all the answers

What is the role of transcription factors in the cell nucleus according to recent findings?

They are responsible for scanning the DNA for their binding sites. Signup and view all the answers

What is often targeted by mutations in cancer cells that affect tumor suppressor genes?

The regions of DNA controlling tumor suppressor gene expression. Signup and view all the answers

What happens to wild-type monomers in the presence of mutant p53?

They can no longer bind to p53 DNA consensus sequences. Signup and view all the answers

What is the primary function of oncogenes?

To promote growth and increased cellular division Signup and view all the answers

Which therapy targets VEGF to inhibit blood supply to tumors?

Bevacizumab Signup and view all the answers

What role do tumor suppressor genes play in cell regulation?

Regulate the cell cycle and DNA replication Signup and view all the answers

What mechanism do agents like Gefitinib and Erlotinib utilize?

Stop signaling pathways that promote cancer growth Signup and view all the answers

Which gene is primarily responsible for the automated cell death process?

Apoptotic gene Signup and view all the answers

What percentage of human cancers is linked to oncogenic activity?

15 to 20% Signup and view all the answers

What do oncogenic viruses typically carry with them?

Viral oncogenes Signup and view all the answers

What function do DNA repair genes serve?

Restoring damaged DNA Signup and view all the answers

How do suppressor genes affect cellular processes?

They slow down division and promote cell death Signup and view all the answers

Which growth factor receptor is associated with oncogenic activity?

Epidermal growth factor receptor (EGFR) Signup and view all the answers

What is the primary role of the Rb gene in the cell cycle?

Inhibits cell cycle activation Signup and view all the answers

What is the consequence of the overexpression of the bcl-2 gene?

Prevents apoptosis Signup and view all the answers

What is the most common target for genetic alteration in human tumors?

Mutated KRAS Signup and view all the answers

What role do fibroblast cells play in the context of mutated KRAS?

They respond to cellular stresses. Signup and view all the answers

Which of the following best describes Knudson’s 'two-hit' hypothesis regarding retinoblastoma?

It explains that retinoblastoma can be either familial or sporadic. Signup and view all the answers

What response does loss of p53 in cells lead to?

Increased Cdk activity Signup and view all the answers

What kind of tissues are considered labile tissues?

Epidermis and gastrointestinal tract Signup and view all the answers

Which cell type is categorized as a stable cell?

Liver hepatocytes Signup and view all the answers

Which of the following is NOT a mechanism of reciprocal signaling from mutated KRAS?

Initiates DNA repair mechanisms Signup and view all the answers

How does mutated KRAS influence neighboring cells?

By altering their behavior through signaling Signup and view all the answers

What occurs as a result of the loss of normal cell cycle control?

Malignant transformation Signup and view all the answers

Which of the following describes the role of the p21 Cdk inhibitor gene?

It suppresses cell cycle progression. Signup and view all the answers

Which of the following proteins is critical in regulating the cell cycle along with the Rb gene?

p16/INK4a Signup and view all the answers

What is the clinical presentation associated with developing retinoblastoma?

Leukocoria, or white reflex in the affected eye Signup and view all the answers

What type of signaling does mutated KRAS engage in with fibroblasts?

Non-cell autonomous signaling Signup and view all the answers

What is one of the essential functions of reciprocity in signaling regarding tumor suppression?

It responds to cellular stresses such as DNA damage. Signup and view all the answers

What aspect of cell cycle regulation does the p53 gene influence?

Regulation of cell growth Signup and view all the answers

What is a characteristic of permanent cells with respect to the cell cycle?

They have lost the capacity to proliferate. Signup and view all the answers

Which of the following is considered a 'brake' on tumor formation?

p53 protein Signup and view all the answers

What is a primary effect of activated signaling pathways in cancer cells from KRAS?

Promotion of cell growth and division Signup and view all the answers

Study Notes

Proto-Oncogenes

Can promote growth and regulation in normal cells.
Typically turned off in adults, but may be turned on by point mutations or chromosomal translocations.
Chromosomal translocations are linked to leukemias and lymphomas.
- Philadelphia Chromosome (Ph1) in Chronic Myelogenous Leukemia.
- t(8:14) translocation in Burkitt’s Lymphoma.
Gene amplification (duplication) results in an increased tendency for neoplasms to have karyotypic abnormalities.

Tumor Suppressor Genes

Their main function is to slow down cell division or cause cells to die at the right time.
They can put brakes on cell cycle progression and DNA replication.
Tumor suppressor genes are DNA repair genes that act as guardians of the genome.
They are the most common target for genetic alteration in human tumors, playing a key role in suppressing tumor formation through two mechanisms:
- Respond to a wide range of cellular stresses, such as DNA damage.
- Activate p21 Cdk inhibitor gene.

p53

If p53 is lost in cells, increased Cdk activity potentially allows for DNA repair.
Loss of p53 can lead to a lack of inhibition of cell proliferation.

bcl-2

Overexpression of bcl-2, activated by translocation, can prevent apoptosis.

Rb GENE

"Governor of the cell cycle," its loss of regulation of cell cycle activation contributes to malignant transformation.
At least one of four key cell cycle regulators (p16/INK4a, cyclin D, CDK4, RB) is dysregulated in the majority of human cancers.

Retinoblastoma

Rare disease where malignant cells form in the retina.
Leukocoria (white reflex in the affected eye) is a common presentation.

Knudson's "Two-Hit" Hypothesis of Oncogenesis

Retinoblastoma can develop either familially or sporadically.
Many tumors possess a point mutation in one TP53 allele, with the second allele being wild-type.
Mutant p53 monomers associating with wild-type monomers alter the conformation of the wild-type monomers, blocking binding to p53 DNA consensus sequences and inhibiting gene transcription.
When only mutant p53 monomers are present, the tetramers cannot bind to p53 consensus sequences in the DNA.

The Cell Cycle

Cells from labile tissues, such as the epidermis and gastrointestinal tract, may cycle continuously.
Stable cells, like hepatocytes, are quiescent but can enter the cell cycle.
Permanent cells, such as neurons and cardiac myocytes, permanently lose the capacity to proliferate.

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Description

Explore the critical roles of proto-oncogenes and tumor suppressor genes in cancer biology. This quiz covers their functions, genetic alterations associated with tumors, and implications for cell regulation and division. Test your knowledge on how these genes contribute to neoplasm formation and chromosome abnormalities.