YW - Molecular Basis of Cancer II

Question 1

What is the role of APC, KRAS, and p53 mutations in colorectal cancer progression? (3)

Answer 1

• Loss of APC: Normal tissue → Early adenoma
• Activation of KRAS: Early adenoma → Late adenoma
• Loss of p53: Late adenoma → Adenocarcinoma

Question 2

What is the function of the p53 tumor suppressor gene? (2)

Answer 2

• Stabilizes the genome, preventing mutations
• Activates DNA repair, cell cycle arrest, or apoptosis in response to DNA damage

Question 3

What are the dual roles of p53 in response to cellular stress? (2)

Answer 3

Reversible Response:

• Activates DNA repair, cell cycle arrest, and senescence for recovery
• Outcomes: Longevity, cell survival, tumor suppression

Irreversible Response:

• Triggers apoptosis, senescence, or differentiation for eliminating damaged cells
• Outcomes: Cell death, aging, neurodegenerative diseases

Question 4

What are the key components of the RAS signaling pathway? (3)

Answer 4

• RTKs: Cell surface receptors activated by growth factors
• RAS: A small GTPase, frequently mutated in cancers
• RAF-MEK-ERK: Kinase cascade amplifying growth signals

Question 5

What is the function of the RAS signaling pathway and its significance in cancer? (3)

Answer 5

• Regulates cell growth, proliferation, differentiation, and survival
• Dysregulation leads to uncontrolled cell growth and cancer
• Therapeutic Targeting: Inhibiting downstream effectors like RAF and MEK

Question 6

What are heterozygous mutations, and how are they identified?

Answer 6

A double peak in sequencing indicates a mutation on one chromosome but not the other

Question 7

What is the impact of KRAS mutations? (3)

Answer 7

• KRAS transmits growth signals to the nucleus, driving cell growth
• Activated by binding GTP
• Inactivated when GTP is hydrolyzed to GDP

Question 8

What is the role of the RB1 gene?

Answer 8

It is a tumor suppressor gene, controlling cell cycle progression

Question 9

What are examples of carcinogens that can cause mutations? (3)

Answer 9

Ionizing radiation: X-rays, UV light

Chemicals: Tar from cigarettes

Viruses:

• HPV (cervical cancer)
• Epstein-Barr Virus (lymphoma, nasopharyngeal carcinoma)
• Helicobacter pylori (gastric carcinoma)
• Hepatitis B (liver cancer)

Question 10

What are the causes of cancer due to environmental and biological factors? (4)

Answer 10

1) UV Radiation:

• Causes DNA mutations, leading to malignant melanoma

2) Tobacco Smoke:

• Contains carcinogens causing DNA damage; leads to lung cancer

3) Viruses:

• HPV: Cervical cancer
• Epstein-Barr Virus: Lymphoma, nasopharyngeal carcinoma
• Hepatitis B/C: Liver cancer

4) Diet and Obesity:

• Chronic inflammation and hormonal imbalances; leads to bowel and stomach cancers

Question 11

What are examples of chromosomal rearrangements in cancers? (3)

Answer 11

Burkitt Lymphoma:

• Translocations: t(8;14), t(8;22), t(2;8)
• Oncogene: c-myc activated by IgH enhancer

Chronic Myelogenous Leukemia (CML):

• Translocation: t(9;22) (Philadelphia chromosome)
• Oncogene: bcr-abl fusion protein, promoting uncontrolled cell growth

Acute Lymphoblastic Leukemia (ALL):

• Translocation: t(9;22)
• Oncogene: bcr-abl fusion protein driving proliferation