Oncogenes and Cancer Biology Exam Review

These flashcards cover key concepts related to oncogenes, their mutations, signaling pathways, and their significance in cancer biology.

What is an oncogene?

• Gene with a gain-of-function mutation

• Promotes uncontrolled cell growth

• Mutations are usually dominant

• Only one allele needs to be mutated

• Often affects genes regulating:

  • Cell proliferation

  • Growth

  • Survival

How can proto-oncogenes become oncogenes?

Proto-oncogenes can become oncogenes through point mutations, gene amplification, chromosomal translocations, or insertional mutagenesis, resulting in overexpression or constitutive activation.

What types of proteins do oncogenes commonly encode?

Oncogenes commonly encode growth factors (e.g. PDGF, EGF), growth factor receptors (e.g. EGFR), intracellular signal transducers (e.g. RAS, BRAF, MAPK, ABL), and transcription factors (e.g. MYC, AP-1).

What are the main steps in the EGF signaling pathway?

1. EGF binds to EGFR, 2. Receptor dimerization, 3. Autophosphorylation of the receptor, 4. Recruitment of GRB2 and SOS, 5. SOS activates RAS by GDP -> GTP exchange, 6. RAS activates RAF -> MEK -> MAPK, 7. MAPK enters nucleus -> activates AP1, MYC, 8. Promotes Cyclin D1/D2 expression -> cell cycle entry.

What is the role of SOS in EGF signaling?

SOS is a guanine nucleotide exchange factor (GEF) that binds to GRB2 via the SH3 domain, replaces GDP with GTP on RAS, and converts RAS into its active form.

How does MAPK affect the cell cycle?

MAPK enters the nucleus and phosphorylates transcription factors such as AP-1 and MYC, activating Cyclin D1 and Cyclin D2, which promotes the G1/S phase transition.

What are Cyclin-CDK complexes and how do they regulate the cell cycle?

Cyclin-CDK complexes are phase-specific regulatory proteins (cyclins) that activate kinases (CDKs), which phosphorylate pRB, releasing E2F to activate genes for DNA synthesis and S-phase; action is stopped by proteolysis of cyclins.

Describe the role of RAS as an oncogene and its mutation frequency.

RAS is an intracellular GTPase in the MAPK pathway; mutations lock it in the GTP-bound active state, found in 90% of pancreatic cancers, 60% of papillary thyroid cancers, 50% of colon cancers, 30% of non-small cell lung cancers, and present in ~20-25% of all cancers.

What is the significance of EGFR in cancer?

EGFR is a receptor tyrosine kinase; overexpression or mutation leads to constant activation and is found in a high percentage of various cancers, including 27-77% of colorectal cancers and 10% of NSCLC mutations.

Why is understanding oncogenes important in cancer biology?

Understanding oncogenes helps explain cancer development, aids in cancer prevention strategies, supports the design of targeted therapies, and enables personalized treatment plans.

Why is KRAS considered a predictive biomarker in colorectal cancer?

KRAS encodes a GTPase downstream of EGFR, is mutated in 35-45% of colorectal cancers, and its mutation correlates with poor response to anti-EGFR therapies, making it useful for predicting treatment outcomes.

What happens when multiple oncogenes are activated together?

Activating multiple oncogenes together leads to faster tumour development; for example, MYC and RAS activation in mice results in aggressive cancer, reflecting the multi-hit hypothesis in human cancer.

How do RNA and DNA tumour viruses contribute to oncogenesis differently?

RNA tumour viruses integrate into the host genome and cause deregulation of proto-oncogenes, while DNA tumour viruses interfere with cell cycle and apoptosis and inactivate tumour suppressor genes.