BRCA1/BRCA2 Mutations
BRCA1 and
BRCA2 are tumor suppressor genes that play a crucial role in the repair of DNA double-strand breaks through homologous recombination. Mutations in these genes can significantly increase the risk of developing breast and ovarian cancer.
BRCA1/2 mutations are inherited in an autosomal dominant fashion, meaning that a single copy of the mutated gene can predispose an individual to cancer.
How do BRCA1/2 mutations lead to cancer?
When either BRCA1 or BRCA2 is mutated, the DNA repair process is compromised, leading to genetic instability and an accumulation of additional mutations. This can eventually result in uncontrolled cell growth and tumor formation.
Who is at risk?
Individuals with a family history of breast or ovarian cancer are at higher risk for carrying BRCA1/2 mutations. Genetic testing is often recommended for those with a significant family history to determine their risk.
What are the implications of a positive test?
A positive test for BRCA1/2 mutations may lead to increased surveillance, prophylactic surgeries, and consideration of chemopreventive agents to reduce cancer risk. It also has implications for family members who might also carry the mutation.
TP53 Mutations
The
TP53 gene encodes the p53 protein, often referred to as the "guardian of the genome." This protein plays a vital role in cell cycle regulation, DNA repair, and apoptosis. Mutations in TP53 are one of the most common alterations observed in various cancers, including lung, colorectal, and breast cancers.
How do TP53 mutations contribute to cancer?
When TP53 is mutated, its ability to control the cell cycle and induce apoptosis is impaired. This allows cells with damaged DNA to continue dividing, leading to the accumulation of additional mutations and cancer development.
What types of mutations are seen in TP53?
Mutations in TP53 can be missense, nonsense, or frameshift mutations. Missense mutations are the most common and often result in a dominant-negative effect or a complete loss of function of the p53 protein.
Can TP53 mutations be inherited? Yes, TP53 mutations can be inherited in a condition known as
Li-Fraumeni syndrome. Individuals with this syndrome have a higher predisposition to a variety of cancers, often at a young age.
What are the treatment implications?
The presence of TP53 mutations can influence treatment decisions. For instance, cancers with TP53 mutations may be more resistant to certain types of chemotherapy and radiation therapy. Research into targeted therapies that can reactivate p53 or exploit synthetic lethality in TP53-mutated cells is ongoing.
