Lecture Notes on Mutations and Cancer

Genetic Mutation and Cancer

• Mutations can affect protein structure and function, leading to diseases such as cancer.
• Gene expression includes making the correct gene product at the right time and amount, which can be disrupted at various levels:
  • Gene transcription
  • RNA processing, export, degradation
  • Translation
  • Protein degradation

Proto-Oncogenes and Tumor Suppressor Genes

• Proto-oncogenes: Genes that promote cell survival or division.

  • Mutations can convert them into oncogenes, which are cancer-causing.
  • Example: Ras family of proteins involved in cell signaling and division.

• Tumor suppressor genes: Limit cell division and promote apoptosis.

  • p53 is a key tumor suppressor, known as the "guardian of the genome."
  • Mutations in tumor suppressors often lead to loss of function, unlike the gain of function in oncogenes.

Effects of Mutations

• Coding region mutations: Can change amino acid sequences, affecting protein structure and function.
• Non-coding region mutations: Can disrupt gene expression regulation, affecting protein levels.

Examples of Genetic Diseases

• Sickle Cell Disease: Caused by a mutation in the beta-globin gene leading to improper hemoglobin formation.

Ras Proteins and Cancer

• Ras proteins are critical in cell signaling, and mutations can lead to constant activation, causing cancer.
• Ras mutations are prevalent in various cancers, especially pancreatic cancer.
• Targeting Ras for cancer therapy is challenging due to complex pathways.

p53 and Cancer

• p53 mutations are common in cancers, usually leading to loss of function.
• Mutations often occur in the DNA-binding domain of p53.
• Loss of p53 function prevents proper cellular response to DNA damage.

Therapeutic Approaches

• Targeting the regulation of p53, like inhibiting the MDM2 protein, can help restore its function.
• MDM2 inhibition increases p53 concentration, promoting its tumor suppressing activities.
• This approach can also reduce chemotherapy side effects by protecting normal dividing cells.

Integration of Course Concepts

• This topic integrates various concepts: protein structure, genetics, enzyme inhibition, DNA mutation/repair, feedback loops, apoptosis, and mitosis.

These notes offer a comprehensive overview of how genetic mutations can lead to cancer, with specific focus on the roles of proto-oncogenes and tumor suppressor genes, and the various strategies for potential treatments.