CBCL 4 Pre-Work

Question 1

Inherited mutations in this mismatch repair gene are found in hereditary non-polyposis colon cancer (HNPCC) syndrome?

Answer 1

MSH2 mutations account for 30% of cases of HNPCC. Other genes in the family of mismatch repair genes that may be affected in HNPCC include MLH1, MSH6, and PMS2.

Question 2

What is true about inherited cancer syndromes caused by inherited mutations in tumors suppressor genes?

Answer 2

Bilateral or multiple tumors are more common than in patients with sporadic inactivation of tumor suppressor genes. Inherited cancer syndromes associated with inherited mutations in tumor suppressor genes lead to cancer in 100% of the affected individuals, since the risk of mutation/loss of the unaffected allele over the lifetime of the individual is 100%. There is a 50% chance of the affected gene being passed on to offspring. Tumors generally develop earlier and are often bilateral or multiple, as compared to sporadic inactivation of tumor suppressor genes.

Question 3

A 4 mm polyp is biopsied from the transverse colon of a 56 year old man. What is the best diagnosis?

Answer 3

Adenoma

The polyp shows increased density of glands and nuclear hyperchromasia, enlargement, and pseudostratification. There is no evidence of invasion. This represents a colonic adenoma.

Question 4

A patient with multiple malignancies is diagnosed with Li-Fraumeni syndrome. Inherited mutations in which genes underlies this diagnosis?

Answer 4

TP53

Inherited mutations in TP53 cause Li-Fraumeni syndrome.

Question 5

Telomerase does what in cancer?

Answer 5

Enables replicative immortaility -Telomerase activation allows cells to replicate indefinitely by regenerating telomeres.

Question 6

What is the role of matrix metalloproteinase in cancers?

Answer 6

Activating invasion and metastasis. Matrix metalloproteinase enzymes are involved in degradation of the basement membrane for invasion.

Question 7

What is the role of VEGF in cancers?

Answer 7

Inducing angiogenesis. VEGF activates angiogenesis in response to local hypoxia.

Question 8

What is the role of PD-1/PD-L1?

Answer 8

Avoiding immune destruction. Tumor cells can upregulate PD-L1 that activates PD-1 on T cells and inhibits T cell activation.

Question 9

What is the role of Cyclin D1 in some cancers?

Answer 9

Sustaining proliferative signaling. Cyclin D1 is a member of the cyclin family and is involved in progression of cell cycle.

Question 10

What is the role of MYC in some cancers?

Answer 10

Sustaining proliferative signaling. MYC is a transcription factor that is over-expressed in many type of cancers.

Question 11

What proportion of cancers are due to an inherited abnormal gene?

Answer 11

A small proportion

Question 12

What are some clinical features of hereditary cancers?

Answer 12

1. Multiple affected relatives
2. Early age of onset
3. Bilaterally affected organs
4. Multiple primary cancers in a single individual
5. Autosomal dominant inheritance

Question 13

How do hereditary cancer syndromes associated with tumor suppressors affect the “two-hit” hypothesis?

Answer 13

In regards to a tumor suppressor gene, the “two-hit” theory relates to how you would need to lose both copies of the gene to have a phenotypic response. In a hereditary cancer affecting tumor suppressors, one copy is already defective so it would only take one mutation to cause it lose function.

Question 14

What is Li-Fraumeni’s syndrome?

Answer 14

Mutation in TP53 tumor suppressor gene. Leading to high incidence of childhood and adult tumors.