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