Carcinogenesis I Flashcards by Lindsey Herrera

The RB protein is hyperphosphorylated in rapidly proliferating cells at ____ of the cell cycle.

S or G2

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__________ and _________ may activate oncogenes or inactivate tumor suppressors.

Translocations; gene deletions

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Autosomal recessively inherited cancers are? (4)

1) xeroderma pigmentosa (XP) 2) ataxia-telangiectasia (AT) 3) Bloom’s syndrome 4) Fanconi’s congenital aplastic anemia (FA)

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Burkitt lymphoma

a cancer of B lymphocytes found in the germinal center

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____ correlates with a poor prognosis in many cancers.

Aneuploidy

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Cancer cell phenotype: _________: lack many of the specialized structures and functions of the tissue in which they grow.

de-differentiated

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Chronic myelocyctic leukemia (CML) is associated with _________ and also see ________.

the Philadelphia chromosome; Burkitt lymphoma

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xeroderma pigmentosa (XP)

ability to repair UV damaged DNA is deficient; cancers occur even after very minimal sun exposure

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What binds to and inactivates the mutant RB protein?

1) SV40 T antigen 2) HPV E7 protein

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What happens to oncogenes in carcinogenesis?

they are activated

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Cancer cell phenotype: ________ : capable of shedding cells that can drift through the circulation and proliferate in other sites.

metastatic

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What is the hallmark of the antioncogene or tumor suppressor gene?

tumor results from a single cell that has acquired homozygosity

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Name 2 tumor suppressors tumors that function by LOH.

1) retinoblastoma (RB) 2) APC gene in FAP

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A _______ is made up of cells that are not invasive or metatstatic, but they have lost ______. They are _____.

benign tumor; growth control and functions of normal cells; immortal

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When there is no RB or when it is nonfunctional, cells cannot ______ and _____.

down regulate the cell cycle; grow out of control

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_____ by CDKs inactivate the RB protein, therefore allowing the cell to proceed from G1 to S.

Phosphorylation

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Cancer cell phenotype: _________: capable of outgrowth into neighboring normal tissues to extend the boundaries of the tumor.

invasive

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Early in life, _______ in somatic cells will produce ____ many years later.

mutagenic events; tumors

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Inactivation of tumor suppressors may occur by ____.

LOH

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What happens to anti-oncogenes/tumor suppressors in carcinogenesis?

they are inactivated

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What is ataxia-telangiectasia?

severe neuro disability coupled with small dilated blood vessels and increased risk of lymphomas and leukemia

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The RB protein is a target for animal tumor viruses, such as ______ and _____.

SV40 and HPV

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What is loss of heterozygosity?

gross chromosomal event that results in the loss of entire genes and the surrounding chromosomal region

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What does XP stand for?

xeroderma pigmentosa

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What does AT stand for?

ataxia-telangiectasia

What is the second hit?

deletion of the second, functional allele

If E7 and E6 expression is blocked, \_\_\_\_\_\_.

the cells return to normal phenotype

The RB protein is hypophosphorylated in _____ cells in G0.

non-proliferating

Autosomal dominantly inherited cancers are? (4)

1) familial adenomatous polyposis (FAP-APC) 2) familial retinoblastoma (RB) 3) familial breast and ovarian cancer (BRCA1 and BRCA2) 4) Wilms tumor syndrome

Aneuploidy

the wrong # of chromosomes

Name the 2 types of genes that allow tumor initiation.

1) oncogenes 2) anti-oncogenes/tumor suppressors

Cells derived from a high frequency of _____ and from ______ carry a defect in the RB gene.

small cell lung cancers; some breast tumors

Philadelphia chromosome

chromosomal abnormality from a 9;22 translocation

Persons who survive inherited RB have an increased risk of \_\_\_\_\_\_, which is usually ______ in origin.

developing a 2nd neoplasm; mesenchymal

Name 4 steps in carcinogenesis.

1) tumor initiation 2) promotion 3) conversion 4) progression

What inhibits p53?

E6 protein

What is an example of a mutagenic event presenting its effects years later?

UV light exposure develops melanoma later in life

The RB protein is a target for \_\_\_\_\_\_.

animal tumor viruses

\_\_\_\_ cells have been growing for 60 years.

HeLa

Tumor initiation occurs by mutations in at least \_\_\_\_\_\_.

2 types of genes

Because RB is an inhibitor of cell proliferation, it is \_\_\_\_.

an anti-oncogene or tumor suppressor

The RB protein is __________ in rapidly proliferating cells at S or G2 of the cell cycle.

hyperphosphorylated

Phosphorylation by ____ inactivate the RB protein, therefore allowing the cell to proceed from G1 to S.

CDKs

What is familial adenomatous polyposis?

polyps in the large intestine that turn into cancer if left alone

\_\_\_\_\_\_\_\_ is inherited.

Susceptibility to cancer

What is the incidence rate of RB?

1:20,000

Cancer cell phenotype: \_\_\_\_\_\_\_\_\_\_: derived from a single cell.

clonal

\_\_\_\_\_\_ is associated with the Philadelphia chromosome and also see Burkitt lymphoma.

Chronic myelocyctic leukemia (CML)

HeLa cells express _____ and \_\_\_\_\_\_.

HPV E7 and E6 protein

Name 3 DNA repair genes.

1) p53 2) BRCA1 3) BRCA2

If \_\_\_\_\_\_\_, the cells return to normal phenotype.

E7 and E6 are blocked

Sporadic cases of RB have _____ retinoblastoma while inherited cases are \_\_\_\_\_.

unilateral; bilateral

The Knudson theory states that ____ are needed to produce \_\_\_\_\_.

two; retinoblastoma

What is the first hit?

a point mutation in one gene

How do SV40 and HPV work?

they drive a quiescent cell into the S phase to proliferate and produce the viral protein

Cancer is related to the accumulation of ______ produced by \_\_\_\_\_\_.

somatic mutations; environmental factors

In RB -/- mice, loss of RB results in \_\_\_\_\_.

pituitary tumors with 100% penetrance

The RB protein is ______ in non-proliferating cells in G0.

hypophosphorylated

A mutation in a _______ increases the rate of obtaining further mutations.

DNA repair gene

Phosphorylation by CDKs \_\_\_\_\_, therefore allowing the cell to proceed from G1 to S.

inactivate the RB protein

anti-oncogenes/tumor suppressor genes

inhibit cellular proliferation

Cancer cell phenotype: _____ to normal signals for proliferation control.

unresponsive

Susceptibility to cancer can be inherited in a _____ or ____ manner.

dominant; recessive

Phosphorylation by CDKs inactivate the RB protein, therefore \_\_\_\_.

allowing the cell to proceed from G1 to S

oncogenes

stimulate cellular proliferation

The RB protein is hyperphosphorylated in _____ at S or G2 of the cell cycle.

rapidly proliferating cells

LOH

loss of heterozygosity

FAP

familial adenomatous polyposis

Aneuploidy correlates with \_\_\_\_\_\_\_\_.

a poor prognosis

E6 protein inhibits \_\_\_\_\_.

p53

Cancer is not inherited as \_\_\_\_\_\_\_.

a single, Mendelian disease