Molecular Basis of Neoplasia CBCL 4

Question 1

What are the types of cancers found in families

Answer 1

1. Vast majority of cancers are sporadic 2. A significant number of them are familial - these have have multigenic pattern of inheritance - these are effected by both genetic and environmental factos 3. Only a very small number of cancers are inherited in a dominant pattern

Question 2

What are hereditary cancer syndromes

Answer 2

These are the ones that have a dominant pattern of inheritance

Question 3

Explain the characteristics of hereditary cancer

Answer 3

1. They affect bilateral organs such as in breast cancer and RB 2. They have an early onset unlike sporadic cancer

Question 4

What genes are associated with hereditary cancer

Answer 4

Tumor suppressor gene

Question 5

Explain the dominant inheritance pattern associated with hereditary cancer and the genes associated with. How is that different from sporadic cancer

Answer 5

Hereditary cancer is inherited in a dominant pattern. Tumor suppressor genes need to be knocked out as both of them need to be out to cause cancer. When an individual inherits hereditary cancer causing gene, only 1 of the tumor suppressor gene may be functional. This undergoes mutation and that leads to early development of tumor in that individual. This is an important concept to know It is different from sporadic cancer since it will take 2 mutations in order to predispose the individual for cancer

Question 6

What type of gene is an RB gene

Answer 6

Tumor suppressor gene

Question 7

What is the inheritance pattern for Rb

Answer 7

Can be both sporadic and hereditary

Question 8

What disease is associated with TP53 gene

Answer 8

Li-Fraumeni Syndrome

Question 9

What are the symptoms

Answer 9

Predisposes the individual to 1. Breast carcinoma 2. Soft tissue sarcomas 3. Brain tumors 4. Osteosarcoma 5. Leukemia

Question 10

What pattern of inheritance is associated with Li-Fraumeni Syndrome

Answer 10

Autosomal dominant or hereditary pattern

Question 11

What is the distribution of colon cancer in terms of its inheritance pattern

Answer 11

Question 12

Exaplin FAP

Answer 12

Familial Adenomatous Polyposis (FAP) is caused by the inherited loss of APC gene. It leads to the development of 1% of all the colorectal cancers seen. The disease has a poor prognosis.

Question 13

What kind of gene is an APC gene

Answer 13

It is a tumor suppressor gene that works with beta catenins to suppress oncogenes

Question 14

What happens in FAP biochemically

Answer 14

There is loss of both ABC gene (one may be lost due to faulty inherited copy like in hereditary cancer). This leads to dysplasia in the colon. Sometime in life these dysplasia will further progress to develop into a benign tumor called adenoma (a benign tumor growth) that appears to be polyps (a protrusion from the muscos membrane). This eventaully becomes malignant cancer.

Question 15

Review: What happens in HNPCC.

How is this disease diagnosed?

Answer 15

In lynch syndrome, a germ line mutation causes proteins associated with mismathc repair to be faulty and this causes the DNA to have faulty corrective machinery that leads to excessive DNA damage.

This can be diagnosed by a technique called microsatellite instability

Question 16

What is the main difference in colorectal cancers that are due to APC gene and the ones that are due to faulty proteins associated with mismatch repair

Answer 16

Colorectal cancers that are due to faulty APC gene display adenomas first that later develop into polyps and then maignant tumor whereas HNPCC does not display adenomas or polyps.