Cancer

Question 0

Burkitt Lymphoma

Answer 0

myc fuzed to immunoglobulin (Ig) (t8:14 crossover)

Level of oncogene expression increased as it is under Ig promotor
lymphocytes fail to develop (undergo rapid cell division)= Cancer

Question 1

Monoclonal

Answer 1

Cancer originating from a single cell.

proof in that cancer cells with have the same X-inactivation

Question 2

Chronic Myeloid Leukemia

Answer 2

Bcr-Abl Translocation resulting in Philadelphia Chromosome (t9:22). Unregulated cytosolic tyrosine kinase (Abl is stuck active)

*Imatinib treatment binds to active site to deactivate the kinase activity

Question 3

Ras Proto-oncogene

Answer 3

GTPase that initiates phosphorylation cascade in cellular proliferation.

point mutation (gly12 or Gln61) Ras becomes constitutively active.

Question 4

Double Minutes

Answer 4

extrachromosomal fragments of DNA containing an amplified region of the chromosome

Ex) EFGR in advanced gliomas

Question 5

Wilm’s Tumor

Answer 5

Results from loss-of-function in the WT1 gene on Chromosome 11, which encodes a transcription factor important in the control of cell growth and differentiation.

Question 6

Two Hit Hypothesis

Answer 6

Mutations needed in both homologs. One is likely inherited requiring only one more ‘hit’ to result in cancer.

Second ‘Hit’ usually not simple mutation but Loss of Heterozygosity (eg. non-disjunction, gene deletion, motic recombination, methylation(epigenetics))

Question 7

Retinoblastoma Gene

Answer 7

Tumor suppressor gene that inhibits E2Fs. E2Fs activate S-Phase Genes.

In Rb disease the Rb gene is absent or mutated resulting in constant expression of S-Phase genes. = cancer

Question 8

Dysplastic Nevus Syndrome

Answer 8

Precursor to malignant melanoma

Mutation in p16 gene responsible for inhibiting CDK that would normally inhibit Rb gene. Results in increased transcription of S-phase genes.

Question 9

p53

Answer 9

Tumor suppressor gene-Activated by ATM & ATR (proteins that scan and detect DNA damage).

• Regulates cell birth/growth (G1/S checkpoint) (activates p21 which inhibits Cln/CDK)
• Can activate Apoptosis in cases of severe damage
• Enhances DNA repair capabilities

Question 10

Li-Fraumeni Syndrome

Answer 10

Inherited mutation of p53. Results in increased risk of cancer at a young age.

First hit inherited by mom. second hit somatic (Loss of heterogeneity)

Question 11

Familial Adenomatous Polyposis (FAP)

Answer 11

Multiple adenomatous polyps (>100) through the distal colon

Mutation in APC gene (WNT pathway) whose role is to down-regulate growth promoting signals

Autosomal dominant (but loss-of-function)
Very high penetrance

Question 12

WNT Signaling Pathway

Answer 12

WNT signal inhibits the destruction complex allowing Beta-Catenin to bind TCF in nucleus to promote growth genes.

Absence of WNT, APC phosphorylates beta-catenin resulting in its ubiquitination and degradation. =reduced growth genes.

Mutation in APC = Cancer. Common in colon cancers

Question 13

Hereditary Non-Polyposis Colon Cancer (HNPCC)

Answer 13

aka - Lynch Syndrome
Mutation in DNA mismatch repair MLH1/MSH2 that results in rapidly progressing polyps. (microsatellite instability)

Autosomal Recessive (but lack of function)

Question 14

BRCA

Answer 14

• found in the cells of breast and other tissue
• involved in DNA repair, mismatch repair or apoptosis

Dominant Inheritance
Allelic Herterogeneity

Question 15

Hercepin

Answer 15

Antibody drug binds to HER2 receptor blocking Epidermal Growth Factor (EGF)

Used to treat HER+ breast cancer tumors.

Question 16

miRNA

Answer 16

Reduce the expression of genes by targeting specific mRNA
Cancer causing if:
1) Reduction in miRNA that inhibit oncogenes
2) Increase in miRNA that inhibits tumor suppressor genes

Question 17

MAP Kinase Pathway

Answer 17

Tyrosine Kinase–> RAS-GTP–> RAF –> MAPK –> Increased Myc