Tumor Supressor Genes

Question 1

Function of Tumor Suppressor Genes

Answer 1

– Transcription factors, cell cycle inhibitors, signal transduction molecules, cell surface receptors, regulators of cellular responses to DNA damage

Question 2

Gene: APC
Protein
Function
Familial Syndromes
Sporadic Cancers

Answer 2

Inhibitors of Mitogenic Signaling Pathways
Gene: APC; 5q21
Protein: Adenomatous polyposis coli protein
Function: Inhibitor of WNT signaling
Familial Syndromes: Familial colonic polyps and carcinomas at very early age
Sporadic Cancers: Carcinomas of stomach, colon, pancreas; melanoma
NF1

Question 3

Gene: RB
Protein
Function
Familial Syndromes
Sporadic Cancers

Answer 3

Inhibitor of Cell Cycle Progression
Gene: RB; 13q14
Protein: Retinoblastoma (RB) protein
Function: Inhibitor of G1/S transition during cell cycle progression
Familial Syndromes: Familial retinoblastoma syndrome (retinoblastoma, osteosarcoma, other sarcomas)
Sporadic Cancers: Retinoblastoma; osteosarcoma carcinomas of breast, colon, lung

Question 4

Gene: VHL
Protein
Function
Familial Syndromes
Sporadic Cancers

Answer 4

Inhibitor of “Pro-growth” Programs of Metabolism and Angiogenesis

Gene: VHL; 3
Protein: Von Hippel Lindau (VHL) protein
Function: Inhibitor of hypoxia-induced transcription factors (e.g., HIF1α)
Familial Syndromes: Von Hippel Lindau syndrome (cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma)
Sporadic Cancers: Renal cell carcinoma

Question 5

Gene: TP53
Protein
Function
Familial Syndromes
Sporadic Cancers

Answer 5

Enablers of Genomic Stability

Gene: TP53; 17p13.1
Protein: p53
Function: “guardian of the genome;” Cell cycle arrest (permanent =senescence) and apoptosis in response to DNA damage
Familial Syndromes: Li-Fraumeni syndrome (diverse cancers)
Sporadic Cancers: most human cancer (mutated in >50%)

Question 6

Gene: WT1
Protein
Function
Familial Syndromes
Sporadic Cancers

Answer 6

Unknown Mechanism
Gene: WT1; 11p13
Protein: Wilms tumor-1 (WT1)
Function: Transcription factor
Familial Syndromes: Familial Wilms tumor
Sporadic Cancers: 
Wilms tumor, certain leukemias

Question 7

Gene: BRCA1, BRCA2
Protein
Function
Familial Syndromes
Sporadic Cancers

Answer 7

DNA Repair Factors

Gene: Breast cancer-1 and breast cancer-2 (BRCA1 and BRCA2)
Protein: Repair of double- stranded breaks in DNA
Function: Repair of double- stranded breaks in DNA
Familial Syndromes:Familial breast and ovarian carcinoma; carcinomas of male breast; chronic lymphocytic leukemia (BRCA2)
Sporadic Cancers: Rare

Question 8

WARBURG effect

Answer 8

Deregulation of cellular metabolism in the presence of oncogenes

Question 9

Glycolysis and cancer

Answer 9

Cancer cells prefer aerobic glycolysis to generate energy and metabolic intermediates; used for rapid growth and cellular components (DNA, RNA, proteins, lipids, organelles

Question 10

Important types of defects of DNA repair mechanisms

Answer 10

o The mismatch repair “spell checkers” (damage from UV light normally; mismatch bt 2 base)
o The nucleotide excision repair (replace abnormal with normal)
o The recombination repair

Question 11

hereditary nonpolyposis cancer syndrome (HNPCC)

Answer 11

a condition of familial cancers of the colon (cecum and proximal rectum) results from defects in DNA mismatch repair genes (the genome “spell checkers”)

Question 12

xeroderma pigmentosum

Answer 12

xeroderma pigmentosum, a condition prone to the development of skin cancer, results from defects of the nucleotide excision repair (NER) pathway

Question 13

ataxia-telangiectasia syndrome

Answer 13

autosomal recessive disorder telangiectasia syndrome caused by a mutation of the ATM gene; results from defects in DNA repair by homologous recombination

Question 14

Tumor progression and heterogeneity

Answer 14

tumors are monoclonal
when clinically evident they are extremely heterogeneous in regards to
- invasiveness,
- rate of growth,
- metastatic ability,
- hormonal responsiveness
- susceptibility to antineoplastic drugs.
tumor consists of many subclones with different characteristics.
Subclones best adept:
-survival, growth, invasion and metastasis.

Question 15

Process of invasion of tumor cell into extracellular matrix

Answer 15

o Detachment of tumor cells from each other
o Attachment to matrix components
o Degradation of ECM
o Migration of tumor cells

Question 16

two hit hypothesis

Answer 16

In hereditary cases the first genetic change (“first hit”) is inherited from an affected parent.

The second mutation (“second hit”) happens subsequently in one of the cells that already carries the first mutation.