Lecture 34

Question 1

How does inflammation increase risk of cancer?

Answer 1

results in persistent regenerative cell proliferation or hyperplasia and DNA damage as a result reactive oxygen and nitrogen species

long unhealed skin wounds characterized by persistent damage can lead to skin cancer

cirrhosis of the liver can lead to hepatocellular carcinoma

Question 2

How viruses may cause cancer

Answer 2

Integration into the genome can cause modulation of oncogenes or tumor suppressor genes

HBV and HCV causes hepatitis which increases the risk of liver cancer through inflammation

Expression of viral genes that alter cellular pathways

Question 3

Sequence of genetic changes associated with colon carcinogenesis

Answer 3

1. Loss of APC gene resulting in hyperproliferative colonic epithelium
2. DNA methylation (promoter) results in loss of expression of other APC gene (2nd hit) resulting in translocation of the b-catenin protein to the nucleus, where it stimulates Myc and Cyclin D transcription. This results in an early adenoma (benign tumor).
3. GOF mutation of ras gene resulting in an intermediate adenoma
4. LOF mutation of the DCC, SMAD2 and SMAD4 tumor suppressor genes resulting in adenoma
5. Loss of mutation of p53 gene and subsequent additional genetic changes. This results in carcinoma

Question 4

B cell infections kept silent by functional T cells

Answer 4

cancers caused by these viruses are frequent observed in AIDS patients and other immunocompromised patients

EBV expresses LMP1 and LMP2 which are cell surface receptors that activate mitogenic signaling pathways

Question 5

Merkel cell polyomavirus

Answer 5

MCPV causes merkel cell carcinoma of the skin

Requires both infection and then mutation of large T antigen to form a truncated version

mostly found in elderly

Question 6

HPV

Answer 6

causes cervical cancer in women of all ages because of the viral proteins E6 targets p53, and E7 targets Rb

Question 7

HTLV-1

Answer 7

produces the TAX protein in the host cell

TAX binds to host proteins to increase the expression of genes that promote proliferation, DNA repair, and resistance to apoptosis

Question 8

Molecular diagnosis of breast cancer

Answer 8

FISH to estimate gene copy number or immunohistochemistry to assess protein expression

BCR-ABL translocation

ER expression in breast cancer correlates with responsiveness to anti-hormone therapy

HER2 overexpression and anti-HER2 antibodies