Carcinogenesis II

Question 1

APC gene and FAP

Answer 1

APC encodes E-cadherin which keeps B-catenin in the PM, APC also helps degrade any free B-catenin in the cytoplasm. Without APC b-catenin goes to the nucleus and promotes trx of oncogenes (c-myc).
Can get polyps. Which with further mutation become cancerous.

Question 2

APC gene id

Answer 2

Positional cloning. Chromosome 5q via genetic linkage and LOH studies. 51% frameshift.

Question 3

BRCA1 and BRCA2

Answer 3

Breast and ovarian cancer. dNA repair. Tumor suppressors. 5% of women have these predisposing genes. They have LOH and only have mutant BRCA 1 and 2.
Frameshift most common.
These genes NOT found in tumor (vs. RB), could be that mutations in other genes affect 1 and 2 indirectly.

Question 4

p53 gene

Answer 4

50% of all cancers. Tumor suppressor. Important for response to environment. 75% missense (NOT frameshift).
Guardian of the genome.
Trx regulator.
Tetramer. Dominant negative (mutant subunit more stable). Why orig. thought to be oncogene.

Question 5

p53 fx.

Answer 5

Trx factor important for gene expression (prevents damaged cell replication).
Required for apoptosis.
Some p53 point mutations are found more frequently in cancer. HOT SPOTS. Prognosis.
Many viruses interfere by inactivating p53 (HPV E6).