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BRCA Mutations and Breast Cancer
BRCA Mutations and Breast Cancer
Ruth Phillips and Patty Ashby
Breast Cancer Breast Cancer
• Most common cancer in women
• Second cause of cancer death in women
• Rates in men???
• Most common cancer in women
• Second cause of cancer death in women
• Rates in men???
BRCA1 and BRCA2 are Oncogenes
• Cancer is caused by mutations in specific oncogenes.
• Mutations in oncogenes change normal cells into cancer cells.
• BRCA1 and BRCA2 are recessive oncogenes.
Sporadic vs Inherited Breast Cancer
• Usually breast cancer is the result of sporadic mutations but about 5% of cancer patient inherit a gene mutation which predisposes them to cancer.
• Tumors develop when a second mutation occurs to make the individual homozygous for the mutation. This is called loss of heterozygosity (LOH).
Increased risk for Carriers of BRCA1 and BRCA2
• Carriers for mutations in these two genes account for:
• 50% of all early-onset cases
• Increased risk for ovarian cancer in women and breast cancer in men
• In families with known cases, risk of developing breast cancer is 80% by age 70
Two Types of Recessive Oncogenes
These genes function as tumor suppressors in normal cells
– Gatekeepers – regulate cell growth
– Caretakers – repair DNA damage
BRCA1 and BRCA2
• Both are caretaker genes
– Code for two different proteins involved in DNA repair
– Large genes with 24 – 27 exons
– Mutations are found throughout the genes with 900 different mutations for each gene
Pictures of 3D Structure of Normal and Mutations
BRCA1 and BRCA2
• Cancer risk is influenced by type of mutation, modifier genes, and environmental and hormonal cofactors
• The risk of developing cancer is not identical for all carriers of BRCA1 and BRCA2 mutations.
• Likewise, the effectiveness of different cancer therapies might vary with the type of BRCA1 or BRCA2 mutation.
Can genetic information be used to:
• predict the best type of therapy for a breast cancer patient?
• develop new individual-based therapies?
Student ProjectSequences from women from two ethnic groups with inherited breast cancer are provided: includes BRCA1 and BRAC2 mutations, and one normal sequence.
Question 1: Compare sequences and look for patterns among the sequences
Question 2: Can you identify mutations that might be causing the disease?
Results of CLUSTALW
Patient 4
Patient 6
Patient 5
Patient 2
Patient 1
Patient 3
Patient 7
Patient 9
Patient 8
Results of CLUSTALW
BRCA1
BRCA1
BRCA1
BRCA1
BRCA2
BRCA2
BRCA2
BRCA2
BRCA2