Genetic Basis Of Cancer Clinical Biochemistrv

Question 1

،،،،،،،، cancer is the most common cancer in men.
• ،،،،،،،، cancer is the most common cancer in women.

Answer 1

Lung

Breast

Question 2

New cells are only formed for:
،،،،،
،،،،،،
Cancerous cells can،،،،،،،،،

Answer 2

growth or
- to replace dead ones.

also destroy the correct functioning cells of the major
organs.

Question 3

Control)of the Cell Cycle

Answer 3

The passage of a cell through the cell
cycle is controlled by groups of proteins:
1. Cyclins.
2. Cyclin-dependent kinases (Cdks).
3. Cyclin-dependent kinases bito (Cdkl).
4.checkpoints
Transition through each phase of cell
cycle is mediated by specific cyclin/cake

Question 4

Checkpoints: 3

Answer 4

G1/S checkpoint.
G2/M Checkpoint.
Spindle Checkpoint.

Question 5

All checkpoints require the service of complex
proteins as:

Answer 5

• P53 protein.
Retinoblastoma protein.

Question 6

Types of Genes that May Causé Cancer

Answer 6

1. Proto-oncogenes and oncogenes.
2. Tumour suppressor genes.
3. DNA repair genes.
4. Genes that regulate apoptosis.

Question 7

• Oncogenic Viruses
Example®

Answer 7

• Oncogenic DNA viruses include EBV, hepatitis B virus (HBV), human papillomavirus (HPV), …
• Oncogenic RNA viruses include, hepatitis C virus (HCV) &human @-cell lymphotropic virus-1 (HTLV-1).

Question 8

Activation of Proto-Oncogenes to Oncogenes,
• by

Answer 8

increasing transcription of their genes.

Question 9

Proto-oncogenes may be activated & converted to oncogenes by five mechanisms?

Answer 9

1- Promoter Insertion: & Certain retroviruses integrate their genome as cDNA in host cells, this
CDNA is flanked by sequences termed long terminal repeats)› that function as promoters for transcription of proto-oncogenes.

2- • Enhancer insertion: The integrated viral genome in host cell may be inserted down stream Or upstream from the proto-oncogene but in the reverse direction.
• Enhancer sequence is present in long terminal repeats

3-Chromosomal Translocations: • A piece of one chromosome is split off and joined to another one. If the second chromosome donates material to the first, then if is reciprocal translocation.
Example:
• Philadelphia chromosome, (chromosome 9
and 22), involved in chronic myelogenous leukemia
- Burkitt Lymphoma The chromosomes involved are 8 & 14.
4- Point Mutation:’Transition & Transversion.
5-Gene Amplification:by administration of the
anticancer drug methotrexate. Tumor cells can become resistant to it by amplification of its gene leading to
increasing the rate of enzyme activity.

Question 10

Mechanism of Action of Oncogenes:

Answer 10

1- May act on key intracellular pathways involved in growth control, uncoupling them from the need to exogenous stimulus.
2-The products of oncogenes may imitate certain growth factors.

Question 11

Oncogenes Can Promote Uncontrolled Cell Proliferation By
Several Mechanisms

Answer 11

-Increase In growth factor
-Increase In growth factor receptors
-Increase in signal transduction
-Increase in activation of transcription

Question 12

¿The human p53 gene is located on

Answer 12

the 17th chromosome (17p13.1), which encodes a protein p53 that plays an important role in cell cycle
control and apoptosis.

Question 13

Protein p53 is a phosphoprotein393 a.as), formed
of 4 domains?

Answer 13

1. A domain that activates transcription factors.
2. A domain that recognizes specific DNA sequences.
3. A domain that is responsible for the tetramerization of the proteins.
4. A domain that recognizes damaged DNA.

Question 14

@Genes promote that are apoptosis
required to as
…….,……
@Genes that inhibit apoptosis as;
…….,……

Answer 14

BAX, BAK,

BCI2
BCL-XL.

Question 15

The Seven fundamental changes in cancer

Answer 15

-Self-sufficiency in growth signals
-Evading apoptosis
-Insensitivity to anti-growth signals
- Genomic instability resulting from defects in DNA repair
- Tissu invasion & metastasis
- Sustained angiogenesis
-Limitless replicative potential

Question 16

Hereditary forms of cancer can be divided into
three categories:

Answer 16

Inherited cancer syndromes.
Familial cancers.
Autosomal recessive syndrome of defective
DNA repair.

Question 17

Hereditary Breast Cancer
• Mutation in two genes,

Answer 17

BRCA1
and BRCA2, account for 80% of
cases of familial breast cancer.

Question 18

Characterized by familiar
carcinoma of the colon affecting ……..,………….

Answer 18

mainly the cecum and the proximal colon resulting from defect in genes involved in DNA mismatch repair.

Question 19

Physical Carcinogens

Answer 19

(1) Ultraviolet rays:
Cause skin carcinoma and melanoma
(2) lonizing radiations:
Cause leukemia
(3) X-rays

Question 20

(3) UV rays and X-rays cause DNA damage:

Answer 20

• Pyrimidine dimers
• Single or double strand breaks
• Cross linkage
• Damage through formation of free
Ladicals in tissues.

Question 21

Carcinogenic Chemicals and Drugs:

Answer 21

• Polycyclic aromatic hydrocarbons: in tobacco smoke → lung cancer
* Azo dyes → cancer bladder
• Aromatic amines
• Nitrosamines : → gastric cancer
• Drugs: cyclo-phosphamide
• Alkylating agents used for Chemotherapy→ cancer
• inorganic compounds: arsenic, lead, asbestos…
• Naturally occurring compounds: Aflatoxin which is produced by aspergillus flavus and contaminate peanuts. • liver cancer

Asbestos → lung cancer & mesothelioma
Vinyl chloride→ liver, brain, lung cancer
Nickel → lung cancer

Question 22

Biochemical Changes In Cancer Celle

Answer 22

• Increased rate of glycolysis, aerobic and anaerobic.
- Change of cell surface glycoprotein, glycolipids.]
- Alteration of cytoskeleton structures like actin filaments.
• Increased secretion of growth factors in the surrounding medium
• Increased activity of ribonucleotide reductase.
• Increased synthesis of DNA and RNA
• Synthesis of fetal proteins e.g carcinoembryonic antigen, AFP.
• Decreased catabolism pyrimidines.
-Inappropriate synthesis of certain growth factors.

Question 23

• P21 binds to Cdk/cyclin

Answer 23

1 • Inhibits Cdk.
2 Prevents phosphorylation of Rb
3° Delays progress into S phase.