Chapter 7 Flashcards
what is a mixed tumor
single neoplastic clone along 2 lineages
what is a mixed tumor of salivary gland
epithelial parts in mixed stroma
what is a pleomorphic adenoma
different size and shapes
what is a teratoma
mature or immature cells of tissues from more than 1 germ line
what are cystic teratomas
differentiate along extodermal line to make cystic tumor lined by skin with hair, teeth etc
what is desmoplasia
a lot of collagen stroma in tumor
what are 2 main parts of any tumor
stroma and parenchyma
what is a scirrhous tumor
stony hard
what is a hamartoma
benign appearing masses made of cells indigenous to a site
what does -oma mean
of msenchymal origin
what is an adenoma
benign epithliela neoplasm from glands
what are papillomas
benign epithelial neoplasms with finger like progections from surfaces
what are polyps
when neoplasm makes macroscopically visible projection
what are sarcomas
arise in mesenchymal tissue and have a fleshy look with little stroma
what is a carcinoma
malignant neoplasm of epithelial origin from any germ layer
what is the most common carcinoma
squamous cell
where do squamous cell carcinomas arise in lung “bronchogenic”
hilar regions centrally
what is a sign of leukoplakia and what should you order
white patches in oral cavity
order biopsy immediatelt
what is anaplasia
lack of differentiation
mitoses of undifferentiated tumors reflects what
increase in proliferative activity or parenchymal cells
what is dysplasia
loss in uniformity of cells and architectural orientation
What is carcinoma in situ
dysplasia changes involving thickeness of epithelium but NOT invading BM
what factors determine rate of growth for a tumor
doubling time of tumore cells
fraction of cells in replicative pool
rate at which cells are shed or die
how do cancer stem cells have high R to conventioinal therapies
low rate cell division and expression of factors like MDR1
What is CML from
malignant counterpart of normal hematopoietic cells
what is AML from
more differentiated myeloid precurors that gain abnormal capacity for self renewal
what cancers do not metastasize
glial cells in CNS gliomas
basal cell carcinoma in skin
what are the pathways of spreading cancer
seeding, lymph , blood
what is pseudomyxomaperitoneal
mucus secreting appendicieal carcinomas filling peritoneal cavity with a gelatinous neoplastic mass
what do you do when detect undifferentiate small cell carcinoma in lungs
close becasue metastasizes and responds well to chemo
where does cancer enter lymph node
subcapsular sinus
where do carcinomas of thyroid and prostate metastasize to
vertebral column
where do renal cell carcinomas metastasize to
renal v, IVC then R heart
where do adenocarcinomas metastasize to
liver, see central necrosis
hispanics are at high risk for what cancers
stomach, liver, uterine cervix and gallbladder
what cause increase cancer
accumulations mutations, decline in immune competence
Describe characteristics autosomal dominant cancer
early onset with increase risk. Usually point mutaiton in TSG
What is retinoblastoma and what kind of cancer is it
autosomal dominant
carry mutant RB allele
what causes familial adenomatous polyposis
mutation of APC TSG
what causes Li-Fraumeni syndrome
mutations in p53
What causes Multiple endocrine neoplasia type 1/2
MEN 1 2
mutations in TF for RET tyrosine kinase
what is HNPCC from
inactivation DNA mistmatch repair gene
What type of pattern are defective DNA repair syndromes
autosomal recessive
examples of defective DNA repair syndrome
xenodermapigmentosum, ataxia-telangiectasia and Bloom syndrome
what is an autosomal dominant form of defective DNA repair
HNPCC
what are the most common familial cancers
carcinomas of colon, breast, ovary and brain
usually b/l
What cancers are common with AIDs
non-hodgkin lymphoma, squamous cell carcinoma, cervical neoplasia, kaposi sarcoma
how can chronic inflammation lead to cancer
immune response becomes maladaptive
what are some precancerous conditions
chronic atrophic gastritis or pernicious anemia, solar keratosis of skin, chronic ulcerative colitis, leukoplakia of oral caivity vulva and penis
what are the 4 classes of normal reg genes
growth promoting proto-oncogenes, growth inhibiting TSG, genes that regulate programmed cell death, genes involved in DNA repair
what type of mutation in a single allel is enough (dominant) to cause cancer
in proto-oncogenes.
TSG you need both alleles
what is haploinsufficiency
loss of genetic function caused by damage to single allele
What is a FLT3 mutation assoc with
constitutive signaling in meyloid leukemia
what type of tumors have active c-kit tyrosine kinase
GI stromal tumors
What R gene is overexpressed in majority cell carcinomas of lung
EGF R ERBB1
What is ERRB2 overexpressed in
breast cancers and human adenocarcinomas in ovary, lung, stomach and salivary glands
What is the single most common abnormalibyt of pro to-oncogenes in human tumors
point mutations in RAS oncogene H K N
mutations in KRAS are what
carcinomas
mutations in hRAS are what
bladder tumors
mutations in nRAS are what
blood tumors
In inactive state what is RAS bound to
GDP
what is the downstrem regulator of RAS
MAP kinase
What does the mutation in RAS cause
GTPase activity, uncontrolled RAS
What is the 9-22 translocation
BCR-Abl fusion cuasing CML and acute lymphoblastic leukemias
polycythemia vera and primary myelofibrosis have point mutations in what
JAK2
What is MYC activation do
apoptosis without survival signals
what causes Burkitt lymphoma
dysregulated c-MYC
what cancers are n-MYC and L-MYC amplified in
neuroblastoma and small cell cancers of lung
activation of cyclin D causes what cancers
breast, esophagus, liver, lymphomas
activation of CDK4s cause what cancers
melanomas, sarcomas and glioblastomas
what is responsible for G1/S checkpoint
p53 via p21 to arrest cell cycle if DNA damage detected
Where is the RB allele
13q14
familial vs spradic RB
familial inherit mutant allele which them mutates other allele
sporadic aqcuire somatic mutation son both alleles
What cancers have genes on short arm CS11
Wilms tumor, hepatoblastoma and rhabdomyosarcoma
What is VHL
TSG that causes familial clear cell renal carcinoma
when is RB active
in hypoPi state
What is RB dependent on to get out of G1
E cyclin
where is the p53 gene
17p13.1
what are the most common tumors from p53 mutations
sarcomas, breast, leukemias, brain, carcinomas of adrenal Cx
What viruses can promote degradation p53
E6 and HPV
what genes regulate p53
MDM2 and MDMX
what does MDM2 do
activates mir34 which binds mRNA preventing translation
ATM and RAD3 (ATR) influence p53 how
Pi it to active so that there is a puase in cell cycle
when DNA repair is successful wha tis role of p53
upregulate MDM2 to destruct and release cell cycle block
what is p63 related to
differentiations of stratified squamous epithelium
what is p73 assoc with
pro-apoptotic effects after DNA damage from chemo
What does the APC gene control
down regulation growth promoting signals
defect in APC gene results in
familial adenomatous polyposis (adenomatous polyps in colon)
describe B catenin- APC pathway
B catenin binds E cadherin resultin gin cell adhesion
loss of contact inhibition by mutation of E cadherin/b catenin are key in what cancers
carcinomas
What type of mutation occur in colon cancer with bcatenin APC zxis
APC fine but mutations in b catenin that prevent destruction APC and accumulation in cytoplasm
What is the role of INK4/ARF
blocks Pi of RB and activates p53 pathway bu inhibiting MDM2
describe TGFb pathway in cell cycle arrest
binds serine-threonine kinase complex dimerization causing Pi SMADs activation p15 and dec Pi RB
what is common mutaion in pancreatic cancer
SMAD4
all pancreatic cancers have a mutation where
in TGFb pathway
What is mutated in cowden syndrome
PTEN
acts as TSG for the pro-apoptotic PI3K/AKT pathway
What happens in NF1 mutation
benign neuroblastomas and optic n gliomas
conversion of RAS from active to inactive
what happens in NF2 mutation
neurofibromin or merlin deficiency
lack of cell cell junctions and insensitivity to normal growth arrest
parth of SWH TSpathway
what type of cancers form with VHL
hereditary renal cell cancers, pheochromocytomas, hemangioblastomas of CNS, retinal angioma and renal cysts
What factor does VHL need
HIF1a do cause degradation
except in hypoxia causes angiogenic GF proliferation
What is from a mutation in WT1
Wilms tumor (kidney) TSG
where is WT1 overexpressed
leukemias and breast cancers
What is PAtched PTCH
TSG of hedgehog
what is syndrome from mutation in PTCH
gorlin syndrome (nevoid basal cell carcinoma)
how do cancers evade apoptosis
inactivate p53 or activate anti-apoptotic genes
pro-apoptotic genes
BAX BAK
what regulate pro and anti apoptotic B proteins
BAD BID PUMA
What is the main antiapoptotic protein
BCL2
hwo do cancer cells accomplish limitless replicative potential
don’t deplete telomerase
What is main cause of epithelial tumors
down regulation E cadherin expression or mutation in catenin
How do tumors degrade BM and interstitial CT
proteolytic enzymes, MMPs, cathepsin D, urokinase plasminogen activator
what direct mobility of tumors
the cytokines (autocrine)
how do tumor cells migrate to selective sites in lymph
CD44
What chemokines for breast cancer are markers for metastasis
CXCR4 and CCR7
what mir promote or suppress metastasis of breast
mir335 and 126 suppress while 10b promotes
What oncogenes promote epithliela to mesenchymal transition
SNAIL and TWIST which encode the TFs needed
Xeroderma Pigmentosum is at increased risk for what
development of cancers of skin follwing UV light because cross linking pyrimidine residues
What are the main metabolic alterations in tumore cells. warburg effect
switch to aerobic glycolysis
what are the advantages of hypoxic conditions for tumors
HIF1a
allows carbons to be shunted to anabolic pathways
what genes cause metabolic changes in tumor cells
RAS, p53 and PTEN
What TSG are mutated in TB
TSC 1 and 2
what type of translocations occur in lymphoid tumors
overexpression of pro to-oncogenes by changing regular elements with another gene
what type of cancers arise from fusion of translocated CCS
hematopoietic, sarcomas, certain carcinomas
What is the translocation if Burkitt lymphoma
8q24 where MYC gene is and replaced with IGH locus with B cell precursor gene
what occcurs from cyclin D1 gene overexpressed on 11q13 by juxtaposition to chrom 14
mantel cell lymphoma
what is the most common translocation of lymphoid malignancies
follicular lymphomas from activation of BCL2 gene
what is the philedelphia chrom
BCR ABL 9-22 translocation
target for leukemia therapy
What causes prostatic adenocarcinoma
translocation in androgen regulate gene and one E family TFs
What type of tumors occur from deletions
nonblood assoc solid tumors
What mutation causes small cell lung carcinoma
3p
what deletions can cause colorectal cancers
17p, 5q and 18q
What cancer is EzH2 overexpressed in
breast and prostate carcinoma repressing TSG p21
leukemias and lymphomas have increased expression of what
BCL2
what are direct acting agents for carcinogenesis
do not need a metabolic conversion and are weak
what are indirect acting agents for carcinogenesis
require metabolic conversion
polycyclic hydrocarbons
benzopyrene
p450 dependent mono oxygenases
people with CYP1A1 genotype are at higher risk for what
lung cancer
What are the molecular targets from carcinogens
RAS, p53
what does aflatoxin B1 do
mutations in p53
What form of UV ray cause cutaneous cancers
UVB 280-320, and the nucleotide excision repair pathway is overwhelmed
what are the most common cancers from ionizing radiation
AML and CML
Describe integration HPV
interupts viral DNA within E1/2 reading farm so lose E2 viral repressor and then overexpression E6 and 7
What is the role of HPV E6 and 7
interact with growth regulatin proteins
E7 HPV has higher affinity for what gene
RB, inactivates CDKIs p21 and 27 then activates cyclin E and A
E6 HPV does what
degrades p53 and BAX
what tumors are more likely in EBV
herpes, burkit lymphoma, B cell lymphoma, gastric carcinomas NK lymphomas
how does EBV get into cells
infects B cells via CD21 C’ R
What proteins does EBV to evade death
MLP1 to actvate BCL2
EBNA2 activates NOTCH
IL10
what is most common child tumor in central africa and new guinea
burkitt lymphoma
nasopharyngeal carcinomas are endemic where
southern china, africa and inuits in artic
HBV causes cancer how
indirect: activates NFkB for apotosis hepatocytes
direct: HBx gene TFs and signal tranduction
Helicobacter pylori is common in what cancers
gastric adenocarcinomas and gastric lymphomas
gastric lymphomas arise from what lymphocyte
B cell origin associated with MALTomas
what is histo fro H. pylori gastric adenocarcinoma
have T reactive cells to H pylori but also poly clonal B cell proliferation
What cells kill latent DNA virus Ag
CD8
what proteins are at higher levels in melanomas
GM2 GD2 and GD3
what protein is higher expressed in breast cancer
MUC1
What IL activat eNK to kill tumors
2 and 15
how do macrophages kill tumors
ROS and TNF
What Ab are used to Tx lymphomas
monoclonal Ab CD20 (B cell)
How do tumor cells evade immune system
loss MHC R lack costimulation for binding T cell inhibitory R CTLA4 Ag masking via glycocalyx Apoptosis CTLs
what cancer is assoc with HMWkeratin
squamous cell carcinoma
how do most neoplasms cause hyper Ca
PTH related protein
what is acanthosisnigircans
gray black patches of verruvous hyperkeratosis on skin
what is hypertrophic osteoarthropathy and what Pts do you see it with
new bone on distal long bones, clubbing of digits
seen with bronchogenic carcinoma
What is trousseau syndrome and what cancers can lead to it
migratory thrombophebitis
usually carcinomas of lung or pancreas
Acute DIC is most common with what
acute promyelocytic leukemia and prostatic adenocarcinoma
nonbacterial thrombotic endocarditis is seen with what
vegetations of mucin secreting adenocarcinomas
What is the grade of a tumor
level of differentiation of tumor and number of mitoses or architectural features
what is the stage of a tumor
size o primary lesion, spread and presence of blood bourne metastasis
What is the TNM rating
T0-4 N0-3 M0-2
when is needle aspiration used
palpable lesions like breast, thyroid and nodes
what is immunohistochemistry used for
determination site of origin and detection of certain R or Ab
flow cytometry is used with what cancers primarily
leukemias
PCR we can differentiate what
monoclonal vs polyclonal
what is comparative genomic hybridization used in
gains/losses tumors
What is the most useful analyses of tmors
molecular progiles
Increased IgG and kappa chain is key to what disease
Mult myelmoa
