Cancer Genetics and DNA Processes

Cancer as an Acquired Genetic Disease

• Cancers are acquired genetic diseases stemming from gene dysregulation.
• Oncogenes and tumor suppressor genes play critical roles in cancer development.
• Mutations are a cause of cancer, altering gene functions.

DNA to Protein Translation

• Genes encode proteins.
• Transcription converts DNA into pre-mRNA.
• Pre-mRNA is processed (splicing) into mRNA (introns removed), leaving only the exons.
• mRNA moves to the cytoplasm for translation.
• Translation converts mRNA into a protein.

Chromatin and DNA Packaging

• DNA wraps around histone proteins to form chromatin.
• Modifications (e.g., acetylation, phosphorylation, methylation) of histone tails regulate the tightness of DNA packaging, impacting gene accessibility.
• Modification of histone tails alters how tightly packaged DNA is and affects gene accessibility.

RB1 Gene and Mutatations

• RB1 is a gene responsible for producing a protein important in regulating cell growth.
• Mutations in the RB1 gene can lead to uncontrolled cell division, contributing to cancer.
• RB1 deletions can remove its tumor suppressor effect.
• Single base mutations in splicing sites can disrupt the gene and result in non-functional RB1.

INK4, a Family of Tumor Suppressors

• INK4 is a family of cyclin-dependent kinase inhibitors.
• INK4 prevents cell cycle progression by inhibiting CDK4/6 and cyclin D.
• INK4 deletions remove the tumor suppressor effect of INK4.

ARF, another Tumor Suppressor

• ARF is a GTP-binding protein, inhibiting MDM2.
• MDM2 enhances the targeting of p53 for degradation.
• ARF deletion removes the tumor suppressor effect of p53.

Philadelphia Chromosome (CML)

• A genetic abnormality specific to chronic myeloid leukemia.
• Characterized by a reciprocal translocation between chromosomes 9 and 22.
• Fusing of ABL1 and BCR genes creates a constitutively active tyrosine kinase.
• Tyrosine kinases can be inhibited by drugs like imatinib (Gleevec).

MDM2 Amplification

• MDM2 is a negative regulator of p53.
• MDM2 amplification (increased copy number), found in several cancers, reduces p53 levels, potentially promoting cancer.

RAS Mutations

• RAS mutations (at codons 12, 13, and 61) in many cancers.
• Leads to constitutive activation of RAS proteins, often associated with uncontrolled cell activity.

TP53 Gene (P53) and Mutations

• TP53 is a critical tumor suppressor gene, involved in cell cycle regulation and apoptosis.
• Frequent mutations in TP53 (more than 70% of cancers) are associated with a loss of its tumor suppressor function.
• Mutations may occur in the DNA binding domain of P53 (30% of cases).