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??? 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 4 Patient 6 Patient 5 Patient 2 Patient 1 Patient 3 Patient 7 Patient 9 Patient 8

Results of CLUSTALW BRCA1 BRCA2