Molecular Biology, Genetics and Immunology of Cancer

Question 1

Original DNA composed of 4 bases

Answer 1

1. Adenine
2. Thymine (In mRNA Uracil substituted)
3. Guanine
4. Cytosine

Question 2

DNA is transcribed by what to RNA?

Answer 2

RNA polymerase

Question 3

Describe translation

Answer 3

Question 4

What are your essential Amino Acids?

Answer 4

Question 5

1. Cell differentiation correlates with loss of ability to ___________;
2. Highly specialized cells are what?

Answer 5

1. proliferate
2. terminally differentiated

Question 6

1. Terminally differentiated cells have a _______ life span,
2. and are replaced with new cells produced from where?

Answer 6

1. finite
2. stem cells

Question 7

_____ _____ are capable of self-renewal; cells divide without undergoing what?

Answer 7

Stem cells

terminal differentiation.

Question 8

1. Normal cell cycle is controlled by what?
2. What binds to surface receptors on the cell?
3. What relay signals into the cell?

Answer 8

1. Signal transduction
2. Growth factors
3. transmembrane proteins

Question 9

What are the two types of growth factors?

Answer 9

1. Growth factors stimulate cell division
2. Growth-inhibiting factors inhibit cell division.

Question 10

What are the cell cycle phases?

5

Answer 10

Question 11

1. Healthy cells divide only when what favors cell division?
2. Cancer cells divide without what?

Answer 11

1. growth factor and growth-inhibiting factor balance favors cell division.
2. constraint (e.g., mutations in growth and growth-inhibiting factor genes).

Question 12

1. All cancer cells contain what?
2. Two categories of cancer genes: dominant and recessive

Answer 12

1. Cancer cells contain genetically altered DNA
   - Hereditary / Germline
   - Somatic / Spontaneous

2.

• dominant termed “proto-oncogenes”
• recessive termed “tumor suppressor”

Question 13

1. Describe Gain-of-function mutations?
2. Describe loss-of-function mutations?

Answer 13

1. Gain-of-function mutations: altered or unregulated activity of a “proto-oncogene” leads to tumorigenesis
2. Loss-of-function mutations: loss of activity of tumor suppressors results in unregulated pathways and tumorigenesis

Question 14

Hallmarks of Cancer?

8

Answer 14

1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evading apoptosis
4. Limitless reproductive potential
5. Capacity to invade other tissues
6. Sustained angiogenesis
7. Tissue invasion and metastases
8. Genomic instability

Question 15

Cancer cells can invade by what?

6

Answer 15

Question 16

Moecular basis of Cancer:

1. Mutations? 3
2. Which genes increase?
3. Which genes decrease?
4. What do these imblances lead to?

Answer 16

1.

• Radiation
• Chemicals
• Virus
  2. Oncogenes
  3. Tumor suppressor genes
  4. Uncontrolled cell growth

Question 17

1. What are Proto-oncogenes?
2. How do proto-oncogenes normally function? 3
3. What kind of cells can they be?3

Answer 17

1. Proto-oncogenes are normal cell proteins that have the potential to cause cancer when mutated
2. associated with cell growth, cell division and cell differentiation
3. can be:
   - cell surface receptors
   - adapter molecules
   - enzymes - kinases/ phosphatases

Question 18

Describe the following cancer types:

1. Carcinoma?
2. Sarcoma?
3. Lymphoma?
4. Germ cell tumors?
5. Blastomas?

Answer 18

1. Carcinoma- epithelial cells
2. Sarcoma- connective tissue cells
3. Lymphoma and Leukemia
4. Germ cell tumors- Testicle and ovary
5. Blastomas- immature cells or embryonic tissue

Question 19

Retinoblastoma (Rb) caused by what mutated gene?

Answer 19

Mutated Rb gene

Question 20

Summary: Methods of identification of cancer critical genes?

4

Answer 20

1. Assay for oncogenic effects
2. Study of rare syndromes-tumor suppressors
3. Candidate genes
4. Genomics: exhaustive surveying is feasible. Identify every change in tumor cell vs. normal

Question 21

Describe the steps in Carcinogenesis?

3

Answer 21

Question 22

Describe the three types of progression in carcinogenesis?

Answer 22

Progression

1. Primary tumor growth
2. Local/Regional spread
3. Distant spread

Question 23

Dividing cells are in what layer of the skin?

Answer 23

basal layer

Question 24

Describe the three steps in Invasion and metastasis?

Answer 24

Question 25

Name A-D?

Answer 25

A. Normal epithelium B. Dysplasia (mutation) C. Pre-malignant (Carcinoma in situ) D. Malignant (Invasive Cancer)

Question 26

What is pictured in the following?

Answer 26

Leukoplakia of the oral cavity: pre-malignant squamous mucosal change

Question 27

What is the following?

Answer 27

Squamous cell carcinoma of the larynx

Question 28

What is the following?

Answer 28

Apical lung mass in a 60 year old lady. Hx of ++ cigarettes and Marijuana.

Question 29

1. Cancer cells grow into a clump and now needs what?

Answer 29

1. its own blood supply

Question 30

Metastasis on a cellular level 12 Steps

Answer 30

Question 31

Distant spread : Metastasis Describe the kinds of spread? 3

Answer 31

1. Spread to other organs through the blood stream 2. Spread to other organs through the lymphatic fluid system 3. Seeding into spaces in the body

Question 32

Sites of metastases of common cancers Breast? 5 Lung? 5 Colorectal? 3 Prostate? 2 Melanoma? 5 Primary Brain? 2

Answer 32

Question 33

Name the regional lymph node drainage in each of the following Primary Cancer Type: ## Footnote 1. Breast? 2 2. Lung? 3 3. Colorectal? 2 4. Prostate? 1 5. Melanoma? 1

Answer 33

Regional Nodal Drainage ## Footnote 1. - Axilla, - Internal Mammary 2. - Hilar, - mediastinal, - supra-clav 3. - Pelvic - mesenteric 4. Pelvic 5. Regional nodes

Question 34

1. Describe local seeding? 2. What spaces for example? 3

Answer 34

1. Local seeding- The cancer has to start in, or invade into a body space. 2. - Abdomen - Lung - Pericardial space

Question 35

1. Normal cell = 23 pairs of chromosomes = 46 = \_\_\_\_\_\_? 2. Cancer cell = Can have less than or more than 46 chromosomes =\_\_\_\_\_\_\_\_\_\_?

Answer 35

1. DIPLOID 2. ANEUPLOID

Question 36

Describe the differentiation, characteristics, and growth rate of each of the following grades: 1 2 3 4

Answer 36

Question 37

Cancer Stem Cell Theory There are two competing visions of tumors. Old cancer model? 3 steps

Answer 37

1) All tumor cells can form new tumors and are therefore equally tumorigenic. 2) Unregulated growth is due to serial acquisition of genetic events leading to the expression of genes that promote cell proliferation with concomitant silencing of growth inhibitory genes and blunting of cell death. 3) Cancer is a proliferative disease.

Question 38

Cancer Stem Cell Theory New Cancer Model? 3 steps

Answer 38

1) Tumors arise from cells termed cancer stem cells that have properties of normal stem cells, particularly self-renewal and multipotent (a minority) of tumor cells. 2) Unregulated cell growth is due to a disruption in the regulatory mechanism in stem cell renewal. 3) Cancer is a stem cell disorder and not a simple mechanism whereby cell proliferation is disrupted.

Question 39

Describe the difference in Cancer Stem Cell Therapy compared to Conventional cancer therapy?

Answer 39

Question 40

1. Conventional chemotherapies kill what? 2. A population of cancer stem cells which gave rise to it, remains untouched and may cause what? 3. Development of specific therapies targeted at the ________ holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease

Answer 40

1. differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate a new one. 2. a relapse of the disease. 3. stem cell

Question 41

What are Cancer Stem Cells? 3 characteristics

Answer 41

Cells that have properties of normal stem cells: 1) The abilities to self-renew. 2) The ability to differentiate into multiple cell types. 3) They form a distinct population in tumors that likely causes disease relapse and metastasis.

Question 42

What are the surgical choices for breast cancer? 2

Answer 42

1. Lumpectomy + radiation 2. Mastectomy

Question 43

Describe the difference in sporadic versus hereditary cancers?

Answer 43

Question 44

Patterns of Hereditary Cancers 4

Answer 44

1. More cancer (of related type) in a family than expected by chance alone 2. Vertical transmission within a family 3. Early ages of onset 4. Multiple primary cancers in one individual

Question 45

Common Hereditary Cancer Syndromes 3

Answer 45

1. Hereditary Breast/Ovarian cancer syndrome 2. Lynch (HNPCC) syndrome 3. Familial Adenomatous polyposis syndrome

Question 46

Which does each of the following affect and what genes are mutated: 1. Hereditary Breast/Ovarian cancer syndrome? 5 organs, 2 genes 2. Lynch (HNPCC) syndrome? 7 organs, 5 genes 3. Familial Adenomatous polyposis syndrome? 6 organs, 2 genes

Answer 46

1. Breast, ovarian, male breast, prostate, pancreatic 2. Caused by mutations to BRCA1 or BRCA2 genes 1. Colon, gastric, endometrial, ovarian, small bowel, pancreas, brain 2. Caused by mutations to MLH1, MSH2, MSH6, PMS1, PMS2 genes 1. Colon, stomach, thyroid, brain, liver, adrenal gland 2. Caused by mutations to APC or MYH genes

Question 47

1. What is lynch syndrome? 2. Which genes are involved? 5 3. **Malignancies may include what? 7**

Answer 47

1. Mismatch repair genes: maintain DNA integrity during DNA replication - Often leads to microsatellite instability in tumors 2. Mutations to 5 different genes (genetic heterogeneity) - MLH1, MSH2, MSH6, PMS1, PMS2 3. colon, stomach, uterine, small bowel, ovarian, ureters, kidney

Question 48

1. Prophylactic Surgery Options for HNPCC-Associated Mutation Carriers 3 2. Surgery does not do what?

Answer 48

1. Options include - subtotal colectomy, - hysterectomy, and - oophorectomy 2. Surgery does not eliminate cancer risk Expert panel made no recommendation for or against surgery due to unproven efficacy\*

Question 49

Surveillance Options for Pts of HNPCC-Assoc. Mutations 1. Colorectal Cancer intervention? 2. Recommendation? 3. Endometrial cancer intervention? 2 4. Recommendation?

Answer 49

Question 50

1. Li-Fraumeni Syndrome (P53 gene)- which cancers? 5 2. Cowden Syndrome (PTEN gene)? 5 3. Peutz-Jeghers syndrome (STK11 gene)? 5 4. Xeroderma pigmentosa syndrome (XP3 gene)? 3 5. Von Hippel-Lindau syndrome (VHL gene) 5 6. Multiple endocrine neoplasia-1 syndrome (MEN1 gene)? 4

Answer 50

1. Breast, bone, leukemia, brain, soft tissue sarcomas 2. Breast, uterine, thyroid, ovarian, colon cancers 3. Colon, small bowel, breast, ovarian, pancreatic cancers 4. Basal cell, squamous cell and melanoma cancers 5. Brain, retina, kidney, pancreas, adrenal gland cancers 6. Pancreas, pituitary, parathyroid, thyroid cancers