Genetics of Cancer

Question 1

proportion of individuals will develop cancer

Answer 1

males 1 in 2

females 1 in 3

Question 2

cancer

Answer 2

a collection of >100 distinct disorders that share the common feature of uncontrolled cell growth.

Question 3

cancer growth is caused by

Answer 3

mutations - changes in DNA that specifically affect genes that incite unlimited cell growth.

Question 4

cancers are what kind of diseases?

Answer 4

genetic diseases

Question 5

cancer development is based on two processes

Answer 5

continuous acquisition ofheritable genetic variation by random mutations.

natural selection which favors cells with mutations which gives them the ability to proliferate and survive better than normal cells.

Question 6

cancer originates follow genetic changes in a _ cell.

Answer 6

single cell.

However, as the cancer cells grow, each cell may have different additional mutations so that the cancer cells differ.

Question 7

two broad categories of cancer

Answer 7

familial (5-10%)

sporadic (mutations)

Question 8

hereditary cancer signs

Answer 8

early onset

transmitted in an autosomal dominant pattern.

Question 9

types of hereditary cancers

Answer 9

breast (10%)
colon >5%
prostate (10%)

Question 10

largest etiologic afactors in cancer

Answer 10

genetics
alcohol
diet
tobacco

Question 11

both sporaid and famililar cancers are caused by

Answer 11

gene mutations

Question 12

types of tumor suppressor (TS) genes

Answer 12

gatekeepers

caretakers

Question 13

oncogene

Answer 13

A mutant allele of a proto-oncogene, a class of normal cellular protein coding genes that promote growth and survial of cells.

Oncogenes stimulate proliferation and inhibit apoptosis.

Question 14

sequence of proto-onco gene function

Answer 14

growth factors secreted -> growth factors bind to receptors -> cytoplasmic signal transduction proteins -> nuclear proteins: transcription factors -> cell growth genes.

Question 15

mutations in signal transduction pathways

Answer 15

activate signal transduction and drive cells into the cell cycle.
c-kit, erb-B, RET, ras

Question 16

mutations of cell cycle regulatory molecules

Answer 16

expedites the G1 - S phase transition as does loss of inhibitory proteins, making cells resistant to differentiation factors.
cyclin D1

Question 17

mutation of transcription factors

Answer 17

actuvate a class of genes required for continued proliferation
(jun, fos)

Question 18

mutation of regulators of programmed cell death

Answer 18

bcl-2

overexpression results in prolonged cell survival and escape from apoptotic signals.

Question 19

how many alleles are needed for oncogenes to be mutated

Answer 19

only one allele needs to be mutated.

Question 20

oncogenes are

Answer 20

gain of function gene

Question 21

ways in which proto-oncogenes can be converted into oncogenes

Answer 21

point mutation
chromosomal translocations
gene amplification

Question 22

example of an oncogene

Answer 22

Ras

it affects transcription factors.

Question 23

Ras

Answer 23

requires a growth factor be activated.

With mutations, Ras is active all the time and cellular growth is unrestrained.

Question 24

in some cases, a proto-oncogene is activated by a

Answer 24

chromosomal translocation (e.g. CML)

Question 25

chronic myelogenous leukemia

Answer 25

results in vast numbers of leukemic cells (granulocytes and megakaryocytes)

Question 26

prrimary event causing myelogenous leukemia

Answer 26

enhanced tyrosine kinase activity

Question 27

activation of proto-oncogene gene by chromosomal translocations

Answer 27

the translocation moves ABL (a tyrosine kinase) to the BCR gene. This causes ABL to always be activated and increases tyrosine kinase activity.

Question 28

Compound which inhibits the BCR-ABL product

Answer 28

imatinib mesylate (gleevec)

Question 29

function of tumor suppressor (TS) genes

Answer 29

they normally block or "put the brakes on" cellular growth. are also cell adhesion molecules involved in comtrol of cell cycle repair mutations in DNA

Question 30

mode of inheritance of mutations in TS genes

Answer 30

recessive. | Function of both alleles must be lost to be cancerous.

Question 31

example of a TS gene

Answer 31

retinoblastoma

Question 32

two hit model of carcinogenesis

Answer 32

two successive mutations (hits) are required to form some types of cancer.

Question 33

gatekeeper

Answer 33

genes that control cell division

Question 34

caretaker

Answer 34

genes that repair DNA damage and maintain genomic integrity.

Question 35

gatekeeper genes encode

Answer 35

regulators of various cell cycle checkpoints | mediators of programmed cell death

Question 36

types of retinoblastoma

Answer 36

sporadic 60% (unilateral) | familial: 40% (most bilateral)

Question 37

mutations in retinoblastoma

Answer 37

first mutation: a point mutation is a point or some other small changes confined to the TS gene. Second mutation loss of all or part of a chromosome.

Question 38

RB1

Answer 38

controls cell proliferation.

Question 39

RB1 gene function

Answer 39

bind and inactivate a group of cellular transcription factors (E2F) which are required for cell cycle progression.

Question 40

hypophosphorylated RB1

Answer 40

inhibits transition from G1 to S

Question 41

As protein (pRb) becomes more phosphorylated, it releases E2F and allows

Answer 41

cells to enter S phase

Question 42

loss of RB protein

Answer 42

If RB gene is missing, E2F is not repressed and regulation of the cell cycle is disrupted and cells undergo more cell divisions.

Question 43

 Germline mutation (inherited diseases):

Answer 43

 Germline mutation (inherited diseases): Inherit one in germ line (first hit inherited) and second hit in a somatic cell (second his acquired)

Question 44

 Somatic mutation (sporadic diseases):

Answer 44

 Somatic mutation (sporadic diseases): Normal germ line, mutation in somatic cell (first hit acquired) and then second mutation in same clone (second hit is also acquired)

Question 45

retinoblastoma second hits are

Answer 45

o Second hits are usually deletions