Cancer

Question 1

Somatic mutations?

Answer 1

oUnderlie all tumors
oMultiple mutations required
oPerturb pathways key in cellular growth, senescence, DNA repair and maintenance, apoptosis, cell cycle, etc.
oDrive uncontrolled growth
oDrive Tissue invasion and metastasis

Question 2

Germline mutations?

Answer 2

oTransmit elevated cancer risk across generations
oUnderlie Hereditary Cancer Syndromes
oInherited from parent (often affected) or arise de novo

Question 3

Two hit hypothesis?

Answer 3

Inherit only one normal gene

One more hit and get disease

Question 4

tumor supressors?

Answer 4

Typically inhibit cellular overgrowth and maintain DNA integrity
•Typically they are inactivated by loss of function mutations in the gene
oNonsense, frameshift, deletions, and others

Question 5

Oncogenes?

Answer 5

•Promote cellular division and growth
•Driven by activating mutations
oMissense changes
oGene Amplifications (Extra copies)

Question 6

Sporadic tumors?

Answer 6

oaccount for the vast majority of cancer

ooccur without marked family history and at usual age

Question 7

Familial cancers?

Answer 7

o15-20% of cancers show familial clustering

omay be due to chance, shared environment, or genes

Question 8

Hereditary cancers?

Answer 8

ohave a recognizable inheritance pattern

oaccount for only 10-15% of cancer, depending on type

Question 9

BRCA 1/2 breast cancer risk?

Answer 9

Breast cancer risk
o~60-80% lifetime risk
•Early Age Onset
•Bilateral Breast Cancer
•Triple negative (BRCA1)
•27% 5y risk for contralateralCA (BRCA1)
•12% 5y risk for contralateralCA (BRCA1)

Question 10

Ovarian cancer risk with BRCA1/2?

Answer 10

o30-45% lifetime risk (BRCA1)

o10-20% lifetime risk (BRCA2)

Question 11

Other cancers with BRCA1/2?

Answer 11

Male Breast Cancer Risk
o1-5% lifetime risk (BRCA1)
o5-10% lifetime risk (BRCA2)
•Pancreatic Cancer
o2-3% lifetime risk (BRCA1)
o3-5% lifetime risk (BRCA2)
•Prostate Cancer Risk
oIncreased –
studies underway

Question 12

Function of BRCA?

Answer 12

DNA double strand repair

Question 13

Function of MLH1?

Answer 13

DNA mismatch repair

Question 14

Function of MSH2?

Answer 14

DNA mismatch repair

Question 15

Function of TP53?

Answer 15

Tumor supressor

Question 16

Function of RET?

Answer 16

Proto-oncogene
Gain of function leads to disease

Tyrosine kinase receptor

Question 17

Function of APC?

Answer 17

Tumor supressor

Question 18

Function of PTEN?

Answer 18

PTEN is a tumor supressor

Phosphorylase

Question 19

What is RB1?

Answer 19

Tumor supressor

Question 20

What is VHL?

Answer 20

Tumor supressor

Question 21

Difference between homo and heteroplasmy

Answer 21

A cell can have some mitochondria that have a mutation in the mtDNA and some that do not. This is termed heteroplasmy. The proportion of mutant mtDNA molecules determines both the penetrance and severity of expression of some diseases.

Homoplasmy refers to a cell that has a uniform collection of mtDNA: either completely normal mtDNA or completely mutant mtDNA.

Question 22

What is the two-hit hypothesis?

Answer 22

The Knudson hypothesis (also known as multiple-hit hypothesis) is the hypothesis that cancer is the result of accumulated mutations to a cell’s DNA.

Question 23

What is loss of heterozygosity?

Answer 23

Loss of heterozygosity (LOH) is a gross chromosomal event that results in loss of the entire gene and the surrounding chromosomal region.

Loss of a copy e.g. Rb

Question 24

What are mismatch repair genes?

Answer 24

Examples of mismatched bases include a G/T or A/C pairing

Repair by these proteins which recognize the parent strain via methylation

Question 25

Proto-oncogene vs tumor supressor gene?

Answer 25

A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. oncogene is a gene that has the potential to cause cancer.[1] In tumor cells, they are often mutated or expressed at high levels