Molecular Basis of Carcinogenesis II

Question 1

FAP is inherited in an _______ fashion, in which patients that inherit one defective _______ gene will be at _______ risk to develop colon cancer

Answer 1

autosomal dominant
APC
higher (90% will develop colon cancer by age 50)
colon

Question 2

Cancer develops when the wild-type gene is lost by _______ in cells in _______ during the first 20 years. Thus, these benign _______ may become malignant

Answer 2

LOH
adenomatous polyps of the colon
adenomatous polyps

Question 3

APC gene was isolated by _______ after it was mapped to chromosome _______ by genetic linkage and _______. The molecular information can be used clinically to identify _______

Answer 3

positional cloning
5q
LOH studies
high-risk patients for therapy

Question 4

APC gene encodes

Answer 4

a cytoplasmic protein that regulates the localization of the Beta-catenin protein

Question 5

Beta-catenin is kept at the _______ by: _______

Answer 5

• plasma membrane

- being bound to E-cadherin in normal cells

Question 6

The APC protein causes _______. When the APC is lost in FAP patients, _______. Thus, loss of APC tumor suppressor causes _______

Answer 6

• the degradation of any unbound and free Beta-catenin in the cytoplasm
• Beta-catenin goes to the nucleus to produce transcription of oncogenes like c-myc
• an overexpression of the c-myc oncogene, resulting in cancer!

Question 7

In Breast and ovarian cancers, there are two similar predisposing genes:

Answer 7

BRCA1 and BRCA2

Question 8

About 5% of woman with breast cancers have inherited mutations in the BRCA1 or 2 _______ genes. These cases therefore display _______ and have _______ genes.

Answer 8

• inherited mutations in the BRCA1 or 2
• LOH
• only mutant BRCA1 or 2

Question 9

the acquired cases, it is believed that _______ may affect BRCA1 and BRCA2 function _______.

Answer 9

• mutations in other genes

- indirectly

Question 10

Both BRCA1 and BRCA2 function in _______

Answer 10

DNA repair

Question 11

BRCA2 has been shown to be allelic with

Answer 11

the Fanconi’s anemia D1 gene, FANCD1

Question 12

individuals with homozygous mutations in BRCA2 get _______, while heterozygotes get _______

Answer 12

• Fanconi’s anemia

- breast cancer from rare recombinant cells in the mammary gland that lose the wild-type allele.

Question 13

p53 is a _______. It also is important for the response of cells to _______.

Answer 13

• tumor suppressor gene

- environmental mutagenesis

Question 14

Cells missing p53

Answer 14

accumulate mutations at a much higher rate and thereby, have a greater chance of becoming malignant.

Question 15

oncogenic p53 mutations produce

Answer 15

a mutant p53 protein that can bind the wild-type p53 protein and inactivate it. These “dominant-negative” p53 mutations can be viewed as “spoilers” or “monkey wrenches”

Question 16

p53 protein

Answer 16

• acts as a transcription factor important for the expression of genes, which prevent cells from replicating damaged or foreign DNA
• is also required for apoptosis, in which cells commit suicide if their DNA is damaged beyond repair

Question 17

In p53 defective cells,

Answer 17

damaged DNA is replicated, thereby producing additional mutations including chromosomal rearrangements, which can lead to cancer

Question 18

mutational “hotspots” produce alterations in amino acids _______ or _______ of p53 in all human cancers

Answer 18

248 or 273

Question 19

an alteration in amino-acid 157 of p53 is found mainly in _______ and is the result of _______

Answer 19

• lung cancer

- the mutagenic chemicals found in cigarette smoke

Question 20

_______ interferes with the life cycle of many human viruses including Adenovirus and HPV (human papilloma virus).

Answer 20

p53

Question 21

Adenovirus and HPV have oncogenes that act by inactivating p53, for example, _______ and _______

Answer 21

Adenovirus E1B and HPV E6 proteins