Intro to Neoplasia and Molecular Basis of Cancer

Question 1

Neoplasm

Answer 1

Clonal proliferation of cells exhibiting uncontrolled growth

Question 2

Malignant neoplasm

Answer 2

Cancer

Question 3

Carcinogens

Answer 3

Cause DNA damage leading to uncontrolled cell growth by acting on specific pathways that control cell growth

Question 4

Benign tumor

Answer 4

• circumscribed
• uncontrolled growth but does not invade adjacent tissue
• well differentiated and resemble tissue of origin
• slow growth rate

Question 5

Malignant tumor

Answer 5

• poorly defined
• infiltrates adjacent tissue
• poorly or well differentiated
• fast growth rate

Question 6

What factors determine tumor growth rate?

Answer 6

• Proportion of dividing cells
• Rate of division
• Ratio of division to death

Question 7

Dysplasia

Answer 7

• Disordered growth usually associated with the epithelium

- May progress to malignant neoplasm

Question 8

Metastasis

Answer 8

• Defining quality of malignant neoplasms

- Spreading requires a repertoire of abilities acquired through accumulation of mutations

Question 9

Routes of metastatic spread

Answer 9

• Lymphatic
• Hematogenous
• Seeding of body cavities

Question 10

Oncogene

Answer 10

• Mutated gene that promotes autonomous cell growth in cancer cells

Question 11

Proto-oncogene

Answer 11

Normal counterpart of an oncogene; essential for cell growth and differentiation and still under normal regulatory control

Question 12

How can a proto-oncogene become an oncogene

Answer 12

• Translocation or transposition to a new promoter => normal growth stimulating protein in excess
• Gene amplification => normal growth stimulating protein in excess
• Point mutation within a control element => normal growth stimulating protein in excess
• Point mutation within the gene => hyperactive or degradation-resistant protein

Question 13

Oncoprotein

Answer 13

Promotes cell growth in the absence of normal growth promoting signals

Question 14

Tumor suppressor genes

Answer 14

Encode proteins that prevent uncontrolled cell growth and division at checkpoints (p53, RB)

Question 15

What kind of mutations are found in oncogenes?

Answer 15

• Activating mutations are usually missense
• Overexpression caused by translocation or amplification
• Activation by translocation and formation of a fusion protein

Question 16

What kind of mutations are found in tumor suppressor genes?

Answer 16

• Loss of function variants

- Deletions

Question 17

Two hit hypothesis

Answer 17

For cancer, both copies of a gene must be damaged

Question 18

Two hit hypothesis: sporadic cancer

Answer 18

Each copy of a gene is damaged individually (sequentially)

Question 19

Two hit hypothesis: hereditary cancer

Answer 19

One damaged gene is inherited and the second copy is damaged individually

Question 20

Tumor testing

Answer 20

• identifies somatic changes
• sample = tumor tissue
• provides diagnostic/prognostic information

Question 21

Germline testing

Answer 21

• identifies germline mutations
• sample = blood or skin cells
• gives info about familial cancer risk

Question 22

Cancer predisposition syndromes associated with mutations in oncogenes

Answer 22

Autosomal dominant:

• Multiple endocrine neoplasia type II
• hereditary neuroblastoma
• costello syndrome
• cardio-facio-cutaneous syndrome
• hereditary papillary renal cell cancer

Question 23

Cancer predisposition syndromes associated with mutations in tumor suppressors

Answer 23

Autosomal dominant:

• retinoblastoma
• li fraumeni syndrome
• hereditary breast/ovarian cancer
• familial adenomatous polyposis
• cowden syndrome - PTEN hamartoma syndrome

Question 24

pRB

Answer 24

• Tumor suppressor gene

- Inhibits G1 -> S transition via a cyclin D-Cdk4/6 mediated mechanism

Question 25

p53

Answer 25

• tumor suppressor gene
• activated by stress: DNA damage, oncogene activation, hypoxia
• induces apoptosis

Question 26

Cancer predisposition syndromes associated with chromosome instability

Answer 26

All are autosomal recessive:

• Ataxia telangiectasia
• Fanconi anemia
• Nijmegen breakage syndrome
• Bloom’s syndrome