cancer Flashcards
cancer?
a bunch of disorders that all have uncontrollable cell growth; they’re all resistant to signals that normally inhibit cell growth
neoplasm/tumor
mass of cells due to uncontrolled cell growth
tumorigenesis
formation of tumors
apoptosis
cell death
angiogenesis
formation of new bv
malignant
tumor that invades nearby tissues
metastasis
tumor that spreads to distant sites
benign
tumor that goes not invade tissue or metastasize
carcinogen
cancer causing agent
process of carcinogenesis?
- cells become resistant to signals that normally inhibit cells growth
- cells disable apoptosis
- new blood supply obtained through angiogenesis nourish tumor
- cancer cells override other signals to become malignant
- tumor metastasizes
how does cancer progress
over time, but when they start to proliferate, progression can occur fast
how are tumors classified?
type of tissue they arise from
carcinoma?
cancer of epithelial tissue
sarcoma?
cancer of CT
lymphoma?
cancer of lymphatic tissue
glioma?
cancer of glial cells of CNS
leukemia?
cancer of hematopeietic organs
all cancer is _________
genetic
what do growth factors do
transmit signals from cell to cell
growth factor receptors?
on surface of cells that bind to growth factors
what do signal transduction molecules do
activate a chain of phosphorylating rxns in the cell changing the activity of different proteins within the cell
where are nuclear transcription factors located? what do they do?
in nucleus; regulate dna transcription by interpreting signals to grow, stop growing, and differentiate
what do tumor suppressor genes do
inhibit cell growth and prevent tumors; block uncontrolled cell growth
what do onco genes do
activate cell growth
retinoblastoma is an example of what type of gene
tumor suppressor
what do onco genes originate from
protoonco genes
mutations in oncogenes lead to what
unregulated cell growth and differentiation
are oncogene mutations gain or loss of function
gain of function
knudsons 2 hit hypothesis refers to: oncogenes or tumor suppressor genes
tumor suppressor genes
what does knudsons 2 hit hypothesis say
cells may have one hit in their germline at birth or the first hit may be somatic
when retinoblastoma gene RB1 is mutated, what occurs
permeant inactivation which means there are no brakes on the cell cycle and cell division is uncontrolled
how many mutations do you need in oncogenes to get a tumor? tumor supressor?
onco- 1
tumor suppressor- 2
leukemias and lymphomas are in oncogenes or tumor suppressor genes?
oncogenes
somatic changes are in oncogenes or tumor suppressor genes?
oncogenes
how can conversion from proto-oncogene to oncogene occur
mutation in dna coding sequence, gene amplification, or chromosome rearrangement
what is HER2/NEU
oncogene amplified in 20-30% of invasive breast cancers
these genes regulate cell growth and proliferation
tumor suppressor genes
these genes promote cell growth and proliferation
oncogenes
these genes behave in a dominant fashion bc you only need one hit
oncogenes
these genes behave in a recessive pattern bc 2 copies of the gene must be mutated
tumor suppressor
3 stages of carcinogenesis
initiation, promotion, and progression
cells can divide_____ times before they can no longer divide
50-70
with each cell division, these shorten
telomeres
when telomeres are shortened to a certain length, what happens
signal is transmitted causing it to no longer be able to divide
telomerase?
gene activated by tumor cells that allow them to replace telomeric segments lost during cell division
telomerase is found in _____% of all tumor cells
85-90%
____ of ppl are diagnosed with cancer at some point in their lives
1/2
____ of deaths are due to cancer
1/4
____% of cancers are hereditary
5-10%
____% of cancers are sporadic
75-85%
____% of cancers are familial
10-15%
____% of ovarian cancers are hereditary
20-25%
high risk for ca based on FHx? low? moderate? (either hereditary, familial ,or sporadic)
low- sporadic
moderate- familial
high- hereditary
why is FH is ca unreliable
many pt dont know the details of their FH like the specific site of the tumor or the age they got it
what is crucial in order to accurately assess the risk of someone getting CA
accurate FH
there is little or no FH in this type of cancer (sporadic or inherited)
sporadic
there are multiple generations with CA in this type (sporadic or inherited)
inherited
this CA usually has a later onset like age 60-70 (sporadic or inherited)
sporadic
this CA usually has an earlier onset like ages 50 or below (sporadic or inherited)
inherited
these cancers are usually single or unilateral tumors (sporadic or inherited)
sporadic
breast or ovarian cancer is usually (sporadic or inherited)
inherited
colon cancer is mainly (sporadic or inherited)
hereditary
what are the causes of colon cancer?
sporadic (65-85%), familial (10-30%), lynch syndrome (5%), and familial adenomatous polyposis FAP (1%)
what is lynch syndrome HNPCC?
early diagnosis of CRC where tumors are mainly in the right/proximal side of the colon; general population is more sporadic and has tumors in the left side of the colon
with lynch syndrome there are other extracolonic cancers families might have. What are these?
endometrium, ovarian, stomach, urinary tract, small bowel, bile duct, sebaceous skin
what is the 321 rule for diagnosing lynch syndrome
3 or more relatives with HNPCC
2 or more generations
1 case of a 1st degree relative of
easier criteria for looking lynch synd
colon or endometrial CA dx under 50yo
colon or endometrial CA dx over 50 yo if pt has a first degree relative with colon or endometrial CA
pt has more than 1 primary lynch synd associated CA
genes associated with lynch belong to the _____ family
mismatch repair (MMR)
mutations in MMR cause what
microsatellite instability
95% of tumors in this disease are microsatellite instability positive
lynch/ HNPCC
what is microsatellite instability
repetitive DNA sequences 1-4 nucleotides (microsatellites) normally found on genome
mmr?
recognize errors in dna repliation
what is missing in the tumor tissue of lynch making immunohistochemical staining useful
mmr proteins
steps in screening for lynch
- screen tumor for MSI via IHC
2. targeted mmr gene mutation analysis
are MMR proteins normally present on immunohistochemistry
yes, if they are absent, the gene is not being expressed
MLH1 and MSH 2 has what type of risk for CA
high
MSH 6 has what type of risk for CA
moderate
PMS 2 has what type of risk for CA
low
MSI and IHC are diagnostic or screening methods
screening
LS management for colon ca
colonoscopy beg at age 20-25 every 1-2 yrs or total abdominal colectomy for colon ca or multiple myelomas/ unresectable polyp
LS management for endometrial ca
annual transvaginal ultrasound (TVU) and endometrial aspitate starting at age 30-35, TAH/BSO after childbearing
inheritance pattern for lynch
AD
is testing kids for adult onset cancer recommended
not unless it’ll affect management
most hospitals do ___ and ____ when they suspect cancer from lynch
MSI and IHC
if we do IHC and see a protein is absent and suspect LS, what should be done next?
direct dna testing on a blood sample
when does the general pop start getting screened for colon ca
age 50
when does someone with a fh of ca start getting screened for colon ca
age10 yrs before relative was diagnosed
GINA stand for?
genetics information nondiscrimatory act
what does gina say
says that health insurance and employers cannot consider genetics as a preexisting condition, but it does not protect an individual from life, long term care, or disability insurance
if someone has 2 mutations in the MMR gene what might they have
constitutional mismatch repair deficiency syndrome (CMMRD)
if someone has LS that was inherited in an autosomal recessive pattern, what may be different about it
they may have childhood presentations of cancers like hematological malignancies, brain tumors, or colon, small bowel, gastric, urologic (same as LS)
what therapy is used to treat colon ca
5 FU adjuvant therapy
this therapy may be beneficial for MSI-H tumors
anti PD 1
this is a common cause of hereditary CRC
LS
familial adenomatous polyposis (FAP) is a ____ type of cancer
hereditary
ppl with familial adenomatous polyposis (FAP) are at risk for what
extracolonic tumors (upper GI, desmoid, brain, thyroid…)
what do untreated polyposis lead to in familial adenomatous polyposis (FAP) ?
100% risk of cancer
estimated penetrance for adenomas in familial adenomatous polyposis (FAP)
90%
MUTYH- associated polyposis (MAP) is what type of inheritance
autosomal recessive
Y179C and G382D are common mutations in this disease
MUTYH- associated polyposis (MAP)
1-2% of the population are carriers for this disease
MUTYH- associated polyposis (MAP)
you can have this condition with no FH bc its autosomal recessive
MUTYH- associated polyposis (MAP)
is breast cancer common
yes, about 1 in 8 women get it
how is breast cancer inherited
autosomal dominant
T or F: cancer on the fathers side does not count
F
ovarian cancer is more likely to be hereditary and many of the hereditary causes of ovarian cancer also increase ones risk for this
breast cancer
is the age of dx or number of women with breast cancer more important in family hx
age of dx
these 2 genes play a HUGE role in hereditary causes of breast cancer
BRCA 1 and BRCA 2
Partner and localizer of BRCA2
PALB2
homozygous mutations in this cause fanconi anemia
BRCA 2 and PALB2
PTEN gene is in this syndrome
cowden syndrome
cowden syndrome greatly increases risk for this cancer
breast
TP53 gene mutation is in this syndrome
Li-Fraumeni syndrome
early onset breast cancer, bone/soft tissue sarcomas, brain tumors, leukemia, adrenocortical tumors are in this syndrome
Li-Fraumeni syndrome
these syndromes affects kids
Li-Fraumeni syndrome and multiple endocrine neoplasia
genes CDKN2A and CDK4 are in this hereditary cancer
familial melanoma
CDKN2A is a _____________ (tumor suppressor or oncogene)
tumor suppressor
CDK4 is a _____________ (tumor suppressor or proto-oncogene)
proto-oncogene
loss of this gene causes loss of p16 activity which eliminates cell cycle regulation
CDKN2A
CDK4 mutation causes a _____ of function
gain
mutation in this gene down regulates pRb causing lack of cell cycle control
CDK4
mutations in these genes can lead to inc risk of melanomas, moles, and pancreatic cancers
CDKN2A and CDK4
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