5070: cancer

what is the hallmark definition of cancer?

uncontrolled cellular proliferation

cancer can be though of as a disease associated with what age group?

older age

cancer is/isn’t a genetic disease?

is a genetic disease

what is the 3 highest modifiable causes of cancer?

• cigarette smoking

• excess body weight

  • alcohol consumption

what is an initiator?

what is a promoter?

causes genetic damage

promotes tumor growth

what 2 things in the diet are protective from cancer?

fiber and antioxidants

what 3 food prep methods are associated w stomach cancer?

pickling, curing, and smoking food

what type of diet is associated with increased risk of cancer?

high fat

what is a neoplasm?

could this be benign or malignant?

a new growth, an abnormal mass of tissue

both

what is the degree of differentiation in a benign tumor?

a malignant tumor?

high

poor

what is the rate of growth in a benign tumor?

malignant tumor?

slow

rapid

what is the local invasiveness of a benign tumor?

and a malignant tumor?

not invasive, usually encapsulated

invasive

what is the distant spread/ possibility to metastasize of a benign tumor?

a malignant tumor?

not able to

metastases common

what is differentiation?

a developmental process where cells gain the capacity for a more specialized function by change of phenotype

what is the general rule about healthy cell differentiation?

once differentiated, they don’t change into a different type of cell

what type of differentiation do cancer cells have?

what does this mean?

poor differentiation

they don’t mature and take on a specific function

when does the malignant phenotype arise?

this results from what two processes?

due to uncontrolled growth

increased proliferation of cells and reduced death of cells

during malignancy, cells lose their _____ features and contribute well/poorly to the function of their tissue

these are also able to _______ and act more like stem cells

differentiated features

poorly contribute

dedifferentiate

what are the 6 basic types of cancer?

1. carcinoma

2. sarcoma

3. myeloma

4. leukemias

5. lymphomas

6. mixed type cancers

where do carcinomas occur?

what % of all cancers are comprised of this category?

epithelial tissues

80-90%

what are some examples of carcinomas?

breast, lung, colon, skin

where do sarcomas occur?

what are 5 examples of this location?

in connective tissues

bones, cartilage, fat, blood vessels, muscles

where does myeloma occur?

in plasma cells in the bone marrow

where do leukemias occur?

what do they cause?

what is this associated with?

cancers of the bone marrow

large # of abnormal blood cells to enter bloodstream

proliferation of immature WBCs, but can also include RBCs

what is another name for leukemias?

liquid cancers

where do lymphomas occur?

in the glands or nodes of the lymphatic system

hodgkin lympoma, non-hodgkin lymphoma

what are multiple myeloma cells?

what do they do?

abnormal plasma cells

build up in the bone marrow and form tumors in many bones of the body

what is typically generated from a multiple myeloma cell?

numerous clones of a single plasma cell

as the # of multiple myeloma cells increases, what product from these cells also increases?

what does this cause the blood and bone to do?

more antibodies

blood thickens, prevents bone marrow from making enough healthy blood cells

what can multiple myeloma also do to bones?

damage and weaken it

what are the rules of grading cancer?

higher the #, more abnormal cells compared to healthy cells

what is a description of a grade 1 tumor?

what are these called/considered?

cells and tissue look mostly healthy

well-differentiated tumors, considered low grade

what is a grade 2 description?

what are these called/considered?

cells and tissues are somewhat abnormal

called moderately differentiated and intermediate grade tumors

what is a grade 3 description?

what are these considered and called?

cancer cells and tissue look very abnormal

considered poorly differentiated, no longer have an architectural structure or pattern

considered high grade

what is a description for grade 4?

what are they called/considered?

the most abnormal looking cells

undifferentiated, highest grade and grow/spread faster than lower grade tumors

what does staging tell us?

what does a higher # mean?

how much the cancer has spread and how large the tumor is

higher # means larger tumor and more distant spread

what does stage 0 mean?

what is this also called?

abnormal cells that haven’t spread and aren’t considered cancer, but could be

in-situ

what does stage 1 mean?

cancer is localized to the tissue of origin

what is stage II?

cancer spread to nearby lymph nodes or other tissues

what is stage III ?

cancer has spread to nearby lymph nodes or other tissues to a greater extent than stage II

what is stage IV?

cancer has spread to other parts of the body (metastasized)

somatic mutations are acquired/inherited and germline mutations are acquired/inherited

somatic: acquired

germline: inherited

sporadic inheritance pattern occurs by ____.

how many of all cancers are sporadic?

chance

95% of all cancers

what are the 3 hereditary inheritance patterns?

• autosomal dominant cancer syndromes

• autosomal recessive

  • familial cancers, uncertain inheritance

what is autosomal dominant inheritance pattern?

what else is normally required for the cancer to manifest?

single copy of inherited mutant gene increases cancer risk

an acquired mutation in the other copy of the gene

what is the pattern of penetrance and expressivity in autosomal dominant inheritance pattern?

incomplete penetrance

variable expressivity

what is the criteria for autosomal recessive inheritance?

how does this increase the risk of cancer?

2 copies of the mutated gene are inherited

greatly increases risk

what are some characteristics of familial cancer of uncertain inheritance?

1. early age of onset

2. predisposition to cancer

3. higher incidence of tumors in relatives

4. mutation in genes that increase risk of cancer

   1. exact genetics unclear

what do most inherited cancers involve? x2 types of genes

tumor suppressor genes

DNA repair genes

what type of gene is not usually involved in inherited forms of cancer?

why is this?

oncogenes

most occur as somatic mutations

what are the 2 general classes of genes that drive cancer formation?

proto-oncogenes and tumor suppressor genes

what is the cancerous function of proto-oncogenes?

act like gas pedals to accelerate cell growth and division after being converted to oncogene

what do cancer-causing tumor suppressor genes do?

they act as the breaks to stop proliferation, but are not able to do this during cancer

in order for cancer to occur, what 2 things have to happen?

1. tumor suppressor genes are turned off

   1. oncogenes are turned on

in a healthy cell, the rate of DNA damage equals what?

how is this different in a diseased cell?

the rate of repair

rate of DNA damage is > than rate of repair

what are proto-oncogenes ?

when are they transformed into oncogenes?

genes that are essential for growth/proliferation

mutations that are activating/gain-of-function

what # of activated proto-oncogene is sufficient to start uncontrolled cellular growth?

one

what are 5 things that proto-oncogenes may code for ?

1. growth factors/receptors

2. cytoplasmic signaling molecules

3. nuclear transcription factors

4. proteins for cell-cell/matrix interactions

what are the 3 ways that proto-oncogenes change to oncogene?

1. point mutation change

2. normal proto-oncogene is overeactive

3. extra copies of normal proto-oncogene in the genome (amplification)

what type of gene is RAS?

what do mutations to this gene cause it to do?

proto-oncogene

remain ‘on’

what is the mechanism of the RAS gene?

when GTP is bound to RAS genes cell division occurs

when GDP is bound to RAS genes, cell division doesn’t occur

what type of cell is Retinoblastoma gene?

what does a mutation cause this to do?

tumor suppressor gene

E2F can perpetually transcribe genes

what is the normal function of retinoblastoma gene?

WHAT IS IT ALSO CALLED?

normally stops cell division by binding to E2F and preventing it from causing gene transcription

THE MASTER BRAKE for the cell cycle

what type of gene is the p53 gene?

what is the result of a mutation to this gene?

tumor suppressor gene

ineffective DNA repair and damaged cells remain

what is the normal mechanism of p53 gene?

p53 protein is made when the cell is stressed

this triggers repair, stalls division and initiates apoptosis if needed

what type of gene is the FANCA gene?

what does a mutation cause?

DNA repair gene

prevention of DNA repair

what are BRCA ½ genes?

what does a mutation cuase?

DNA repair gene

prevention of DNA repair

what is the normal mech of FANCA gene?

protein part of Fanconi anemia pathway that is triggered when DNA damage is detected

what is the normal function of BRCA1/2?

play a role in DNA repair

how many copies of ts genes are inactivated when cancer develops?

2

what is the ‘two hit hypothesis’?

germline mutation of ts gene inherited leads to much higher risk for cancer development

what are the 2 ts genes?

RB and TP53

the p53 protein is a cellular _____ monitor.

it is the most/least common ts gene defect in cancer cells

what is the p53 protein also called?

stress

most common

“guardian of the genome”

cells with mutant p53 proteins are unable to do what 2 things?

conduct efficient DNA repair

undergo apoptosis when needed

in the inactive/active state, DNA repair genes contribute to cancer.

how many copies have to be affected when cancer develops?

inactive

both

what type of mutation (somatic/germline) of BRCA is associated with increased risk of breast cancer?

what types of cancer are associated with this?

germline

breast, ovarian, prostate

are most cases of breast cancer caused by inherited genetic mutations?

no

when a normal cell is transformed into a cancerous cells, the proteins involved in regulating cell division events no longer appropriately _______ ________ from one stage to the next.

drive progression

what are the rules of appropriate progression from one cell division stage to the next

proceed to next stage of cell cycle only when needed and only if everything is ok

what are 4 mechanisms that help a normal cell be transformed to a cancerous cell?

1. proteins of cell division

2. oncogenes

3. TS genes

4. DNA repair genes

what are the 4 cell cycle checkpoints ?

1. spindle assembly checkpoint

2. G1 checkpoint

3. S phase checkpoint

4. G2 checkpoint

what does the spindle assembly checkpoint confirm? x 1 things

the chromosome attachment to spindle

what does G1 checkpoint check for? x 4 things

what happens if this doesn’t pass the check?

• cell size

• nutrients

• growth factors

• DNA damage

resting state

what does the S phase checkpoint confirm? x 1 thing

if there was DNA damage at the G1 checkpoint, that it was repaired.

what does the G2 checkpoint examine? x2 things

what happens if it finds problems?

cell size, DNA replication

resting state

what is a karyotype?

the # and visual appearance of the chromosomes in the cell nuclei of an organism/species

what are 3 types of large karyotypic changes?

what mutation causes a subtle change ?

translocation, deletion, amplification

point mutations

what does a point mutation do in a RAS gene?

what type of function does this cause?

over-activates the protein

gain-of-function mutation

what does a point mutation cause in an RB or P53 gene?

what type of function does this cause?

reduces/abolishes their function

loss-of-function mutation

what is translocation definition?

what 2 things could it cause in the cell?

exchange parts of nonhomologous chromosomes

1. overexpression of proto-oncogene

2. creation of novel fusion protein

what is a deletion?

what happens if this happens to a section of TS genes?

whole or portions of chromosome lost

cancer results

what are gene amplifications definition?

what could this lead to in a normal proto-oncogene?

several hundred copies of gene on chromosome

overexpression of normal proto-oncogene

what is an example of a gene amplification in real life?

HER2 gene coding for HER2 receptor- signals cells to grow and divide

HER2 is amplified in 20% of breast cancer → cells signaled to grow and grow

what is herceptin?

a monoclonal antibody drug that blocks growth signaling from HER2 pos breast cancer

with what 2 epigenetic conditions would a tumor suppressor gene be poorly expressed?

highly methylated

in heterochromatin region

in what 2 epigenetic conditions would a proto-oncogene be highly expressed?

hypomethylation

in euchromatin

what 2 proteins does HPV make and what do they do to RB and p53 proteins?

E6: degrades p53

E7: disables RB from binding to E2F promoter and halting cell division

sustained proliferative signaling means that the cells should do what?

keep dividing

during evasion of growth suppressors, what happens to TS genes and cell cycle checkpoints?

inactivation of TS genes

checkpoints are non-functional

during the hallmark “resisting cell death”, tumors result more from _____ cell death than ____ cell proliferation

reduced cell death

increased cell proliferation