Download Results of CLUSTW

BRCA Mutations and
Breast Cancer
Ruth Phillips and Patty Ashby
Breast Cancer
• 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 Project
Sequences 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 7
Patient 3
Patient 1
Patient 4
Patient 6
Patient 5
Patient 2
Patient 9
Patient 8
Results of CLUSTALW
BRCA2
BRCA2
BRCA2
BRCA1
BRCA1
BRCA1
BRCA1
BRCA2
BRCA2