cancer genetics

Question 1

familial cancer

Answer 1

inherited from family …

family has a predisposition through a germ line mutation
which increases the prob that further mutations will occur

Question 2

sporadic cancers

Answer 2

new mutations arising in the somatic cells of the body

Question 3

properties of cancer calls

Answer 3

autocrine stimulation: grow in the absence of growth factors

lack of gap junctions: lack of “communication”

resistance to cell death

rapid growth: presistent telomerase activity

angiogenesis: capilary growth

clonal

accumulation of successive mutations

Question 4

cell proliferation rates

Answer 4

slow : bone nervous system

fast: RBC

age dependent proliferation: retinoblast

Question 5

oncogenes

Answer 5

Genes that induce cell division . Gain of function
mutations

Mutations results in abnormal stimulation of cell division
and proliferation

They are dominant so single mutation i sufficient to cause change

Question 6

tumor suppressor genes

Answer 6

–Genes that suppress cell division

Loss
of function mutations.

Question 7

pro- and anti-apoptotic

Answer 7

A related category is genes that induce cell death through a

program called apoptosis.

Question 8

Chromosomal translocations

Answer 8

cause mis-expression of

genes or create chimeric genes also cause cancer

Question 9

MEN2

Answer 9

Multiple Endocrine Adenomatosis, Type 2

mutation in the RET( tyrosine kinase)
gain of function causes cancer of endocrine glands (thyroid and endocrine)

Question 10

burkitt lymphoma

Answer 10

t(8;14) affects MYC casues more proliferation

Translocation of cmyc from chromosome 8 to chromosome 14, adjacent to the immunoglobulin heavy chain gene locus. Overexpression of cMyc.

Question 11

Chronic Myelogenous Leukemia

Answer 11

(Philadelphia chromosome): t(9; 22) (q34; q11): BCR-ABL chimeric gene, has tyrosine kinase activity.

Question 12

Acute Promyelocytic Leukemia

Answer 12

t(15;17)(q22;q11): PML-RARα chimera

characterized by a proliferation of malignant
promyelocytes in the bone marrow

PML–RAR has dual effects.
– It causes apoptosis resistance.
– it blocks the transcription of RAR target genes. PML–RAR
homodimers bind tightly to transcriptional corepressors, which
attract histone deacetylases (HDACs)

Question 13

Follicular B-cell Lymphoma

Answer 13

Primary abnormality in B-cell lymphoma is over expression of the anti-apoptotic protein, Bcl-2, caused by a t(14,18)(q32q21) translocation.

Bcl-2 prevents release of cytochrome c, an essential component for apoptosis.
• Translocation brings Bcl-2 under the control of the
immunoglobulin heavy chain locus and the Bcl-2 locus.

Question 14

telomerase as oncogene

Answer 14

telomerase is a reverse transcriptase responsible for lengthening telomeres

Telomerase activity dwindles with every cell cycle eventually causing cell death

telomerase expression reappears in cancer cells indefinitely

Question 15

Two hit hypothesis

Answer 15

retinoblastoma as an
example: hereditary vs. sporadic forms: bilateral,
early onset for the former, unilateral, late onset for
the latter.

• Second hit is mostly a somatic mutation, mostly
caused by Loss of heterzygosity.

Question 16

mechanisms of second mutation

Answer 16

can happen via

epigenetic silencing

mutations

somatic recombination

loss and duplication

chromosome loss

Question 17

Cancers caused by Tumor Suppressor

Gene Mutations

Answer 17

familial polyposis coli,
breast cancer, hereditary non polyposis colon carcinoma
and Li-Fraumeni syndrome involve tumor suppressor
genes

Question 18

Retinoblastoma

Answer 18

loss of function tumor suppressor gene

can cause other cancers with one additional mutation

Question 19

RB1

Answer 19

p110 cell cycle regulation

Question 20

gate keepers

Answer 20

directly regulate genes

eg p53 and retinolblastoma

Question 21

caretakers

Answer 21

a defect in a caretaker is not likely to provide a selective advantage but rather leads to mutaitons of gatekeepers

Question 22

Regulation of G1 to S
Progression by
Retinoblastoma Protein

Answer 22

pRB binds to transcription factors inhibiting from binding to DNA inhibing transcription from G1–>S

cyclin cdk phosphoralates pRB and frees up the transcription factors which activiates transcription

pRB mutated causes no supression of trancription factors to DNA

Question 23

P53

Answer 23

gatekeeper

DNA binding protein important in cellular
response to DNA damage.

also triggers apotosis pathway if too much damage

Loss of p53 thereby allows cells with damaged
DNA to survive and divide

Question 24

Mechanism of
G1 Arrest
Caused by DNA
Lesions

Answer 24

p53–> promoter –>activates WAF1—> produces p21(cdk inhibitor) —–> makes complex with cyc cdk and causes blockade transition from g1 ti S due to no phosphorylation of pRB

Question 25

Apoptosis

Answer 25

A trigger sets off a series of events, including:
– cell shrinkage
– activation of endonucleases that chew up DNA
– mitochondrial damage that prevents energy generation
– activation of a class of proteases called caspases that
proteolytically cleave intracellular proteins required for
cellular function and infrastructure.
– The cells are engulfed by neighboring cells and
macrophages without generating an inflammatory
response.

Question 26

Familial Breast Cancer: BRCA1 & BRCA2

Answer 26

BRCAmutations account for a majority of autosomal dominant familial

breast cancer Caretaker genes tummor suppressor genes take part in DNA repair

Question 27

Hereditary non polyposis colon cancer

Answer 27

Inheritance:autosomal dominant. Group of 5 similar cancersyndromes, caused by one of 5 distinct DNA repair genes:
MLH1, MSH2, PMSL1, PMSL2, MSH6

Caretaker genes. Two hit hypothesis in play. Result is
genomic instability and mutations of other genes.