Oncogenes and Tumor Suppressor Genes Podcast

Question 1

oncogenes:

Answer 1

genes that promote autonomous cell growth. Gain of function mutation must occur by either change in STRUCTURE or REGULATION of expression to become proto-oncogene (cancerous).

Question 2

5 classes of oncogenes

Answer 2

1. Growth Factors (autocrine loop not systemic)
2. Growth Factor Receptors
   (hyperactive)
3. Proteins involved in signal transduction
4. transcription factors
5. cell cycle regulators (cyclins)

Question 3

ERB-B2 and HER-2x

Answer 3

Oncogene. Human Epidermal Growth Factor Receptor-2 that is amplified/overexpressed in Breast cancer

Question 4

RAS

Answer 4

oncogene. most common kind of mutation seen in cancer.

Question 5

BCR/ ABL translocation in myelogenous leukemia

Answer 5

oncogene. Chimeric gene produced

Question 6

C-MYC

N-MYC

Answer 6

oncogenes
C-MYC: overexpression causes Burkitt Lymphoma due to translocation

n-MYC: over expression causing neuroblastomas

Question 7

Gatekeeper genes:

Answer 7

BOTH allels need to be inactivated

• deletion of gene or chromosome
• gene loss and reduplication of chrom
• mitotic recombination
• methylation ofg promotor

Question 8

Rb (Retinoblastoma)

Answer 8

Tumor supressor gene.

Normally inhibits transcription by binding to transcription factor E2F

Release of E2F allows transition of S phase

• ->NORMALLY: p 105Rb is phosphorylated to cause release. OR
• -> PATHOGENIC RELEASE: p 105Rb inactivated by viruses or complete loss of p 105Rb

Question 9

Familial Rb vs. Sporatic

Answer 9

Familial:

• early in life
• one bad allele inherited
• bilaterally

Sporatic:
-requires 2 bad alleles

Question 10

TP53

Answer 10

Tumor supressor gene.
Most common genetic defect in human neoplasms.
NORMALLY: Accumulation of TP53 protein = cell cycle arrest, senescence, apoptosis, or activation of DNA repair genes

PATHOLOGY: p53 pathway inactivated by mutation, regulation is abnormal, or p53 products inactivated by virus

Question 11

APC

Answer 11

Tumor suppressor gene. NORMAL: binds to and inhibits b-catenin

Pathology:
familial = adenomatous polyposis coli

sporadic = colorectal cancer

Question 12

Li-Fraumeni Syndrome

Answer 12

1 abnormal copy of TP53 is inherited. Sporatic mutation in gene occurs early. likely to have breast cancer or sarcoma

Question 13

FAP (Familial Adenomatous Polyposis)

Answer 13

Inherited loss or mutation of APC gene. (APC is a tumor supressor gene that works with beta catenin to repress transcription factors)

Question 14

HNPCC (herditary nonpolyposis colorectal cancer) AKA Lynch Syndrome

Answer 14

Germline mutations in one (or more) mismatch repair genes (microsatellite instability)
●MLH1 (MutL homolog 1), which is located on chromosome 3p21
●MSH2 (MutS homolog 2), which is located on chromosome 2p16
●MSH6 (MutS homolog 6), which is located on chromosome 2p16
●PMS2 (postmeiotic segregation 2), which are located on chromosome 7p22

Question 15

How does sporatic defect in APC gene differ from inherited defective APC gene?

Answer 15

sporatic defects in the APC gene are usually a result of epigenetic methylation of the promotor region.

Question 16

Oncogene:
ERBB1 (EGFR)
ERBB2 (HER)

Answer 16

Growth Factor Receptors

EGF-receptor family

Question 17

Oncogene:

BRAF

Answer 17

RAS signal transduction. Point mutation, Translocation

Question 18

Oncogene:

JAK2

Answer 18

JAK/STAT signal transduction. Translocation.

Question 19

Oncogene:

CDK4

Answer 19

Cyclin-dependent kinase Amplification or point mutation

Question 20

CCND1

Answer 20

affects Cyclin D1, cell cycle regulator