4. Cancer I Flashcards
• ____ can tell you about risk factors, about what to look for and trends
○ Informs healthcare decisions
• ____ is the process that the cell goes through from being normal to being cancerous
• Cancer designates a ____ growth (an invasive form versus the benign growths)
○ ____ - a new mass
epidemiology
carcinogenesis
malignant
neoplasm
Fundamental Characteristics of Cancer
Change in cellular genetic material
____, epigenetic
____, induced, and/or inherited
• Mutations ○ A change in AA, or a change in the bigger part of gene that affects function • Epigenetic signatures that control genes can be affected ○ Considered to be a change in \_\_\_\_ material ○ Changes that are on the DNA that will dictate whether a gene will be turned on or silent § \_\_\_\_ § \_\_\_\_ that bind DNA and compacted into chromatin - can be modified ○ Change in epigenetics in a gene will result in it being activated or silenced • Inherited - comes from the \_\_\_\_ (sperm/egg) ○ Not a majority of cancers (\_\_\_\_%) • Spontaneous/induced - 90% ○ Somatic cells can accumulate mutations (spontaneous) Or, in the presence of UV light, tobacco, alcohol use (\_\_\_\_)
mutations
spontaneous
genetic methylation histones germline 10 induced
Fundamental Characteristics of Cancer
Changes are heritable by daughter cells
____ selection
Tumors are ____
• Cancer can be passed down onto daughter cells ○ An initial cell has change in genetic material, and upon dividing it passes it on § Inheritable change § Darwinian selection - the most \_\_\_\_ survive; cancer cells survive indefinitely □ Mutation that allows cell to survive under low \_\_\_\_; manipulate the oxygen supply to cancer to overcome the advantage the cancer has ○ Tumors are clonal § Tumor doesn't mean bad/malignant, just that there is \_\_\_\_ § There was one initial cell that acquired a mutation/epigenetic change that allowed it to survive □ Clonal □ Especially true early during growth period; however, later on there can be subclones that develop (arise by accumulating more mutations, etc.) ® Will eventually become a \_\_\_\_ grouping of cells
darwinian
clonal
fit
O2
growth
heterogeneous
Hallmarks of Cancer
Independence of ____
Resistance to growth inhibition
Evasion of ____
Limitless replicative potential
Acquired ____ potential
Transplantability and invasion
Switch to ____ despite O2
Immune evasion
• Cell acquires mutations so it's not hindered by external cues: • Somatic cell has limited number of cell divisions ○ 25-28 divisions - enters \_\_\_\_ ○ Cancer cells devise a way around this by modulating telomere lengths § Become immortal • Angiogenic potential ○ Not a \_\_\_\_ process - it's imperfect • The last three hallmarks are more critical in context of \_\_\_\_ potential • Switch to glycolysis ○ Usually it's anaerobic, but cancer cells switch in the presence of O2 • Normally recognized as foreign, but cancer cells find a way to hide from the immune system
growth factors
cell death
angiogenic
glycolysis
senescence
physiological
malignant
• Neoplasia
○ New ____
○ Nothing about it being benign/malignant
• Transformed cell
○ Changing ____ type
○ Tobacco smokers
§ Bronchial epi changes from columnar to ____ epi
• Tumor and neoplasm can be used ____
• Benign tumor
○ Can be fairly certain that upon removal it won’t come back
○ Contained within a ____, or a capsule-like border from the surrounding tissue
§ Reason why upon removal you can be pretty sure it can be ____
§ Some tumors do not have capsules: ____
□ Smooth muscle benign tumor in uterus
□ There is still a zone that is visible by eye
• Malignant tumor
○ Will not have any ____
○ Cells begin infiltrating surrounding tissue
§ Not only to lymph node, but even local invasion is considered a sign of malignancy
growth cell squamous interchangeably capsule removed leiomyoma capsule
• Benign tumor
○ Grows locally, cannot spread by invasion/metastasis
• Malignant tumor
○ Can invade neighboring tissue, and rare cases it will go to distant organs
§ Can occur via BV, local spread, or lymphatics
• Benign growths can turn ____
○ A single mutation will join by other mutations, and the cells will gain additional advantages that will allow them to proliferate further
• Is a benign tumor always precancerous?
○ Not always!
○ Varying ____ to become malignant, but for some the risk is high (in ____ users, for example; in lyomyoma, it rarely ever becomes malignant)
○ Can be considered precancerous with various degrees to become malignant
malignant
potentials
tobacco
• Left: benign tumor
○ Cannot based on size, small can be ____, and vice versa
○ Fibrous growth - ____
• Middle: ____
○ Under skin there are BV that make it look pink
○ Benign tumor; if excise it’s ____
• Right: ____
malignant fibroma hemangioma curative lipoma
• Large benign tumors can still lead to issues
○ Benign doesn’t mean that it’s not going to lead to complications
• Abdominal mass from a 10 y/o patient
○ ____, upon removal the patient will be ____
○ Can still lead to clinical problems
encapsulated
cured
• Benign tumor pathology
○ ____
○ These examples are colon polyps
○ Well structured and ____
capsules
bordered
Malignant tumors
• The edge is not \_\_\_\_ • Middle: malignant melanoma ○ \_\_\_\_ borders • Right: malignant melanoma ○ Scar tissue on the top
clear
irregular
Benign Tumor Nomenclature
Normally end with –____ Lipoma
Leiomyoma
Exceptions
____ can be either
Lymphoma, melanoma, mesothelioma, seminoma are ____
Epithelial tumors are even more complex \_\_\_\_ – gland patterns/gland origins \_\_\_\_ - fronds \_\_\_\_ – mass above a mucosa \_\_\_\_- - hollow masses
• Mesenchymal tissue - ends with -oma • Blood cancers are all malignant • \_\_\_\_ tumors based on how it looks to eye ○ Papilloma - extensions, finger-like projections • Sometimes depends on histological pictures ○ Adenoma - glandular patterns • Polyp ○ Benign tumor ○ Distinctive \_\_\_\_ that's attached to base
oma astrocytoma malignant adenoma papilloma polyp cystadenomas
epithelial
stalk
Malignant Tumor Nomenclature
Solid mesenchymal tumors
____
Tumors from blood cells
Leukemias
____
Epithelial tumors
____ (regardless of ____ origin)
— Adenocarcinoma
— Squamous cell carcinoma
• Leiomyosarcoma - from the muscle
sarcoma
lymphomas
carcinoma
tissue
Mixed Tumor
\_\_\_\_ differentiation Mixture of different \_\_\_\_ types Pleomorphic adenoma -- Epithelial \_\_\_\_ tissue -- Fibromyxoid \_\_\_\_
• Usually tumors arise from one germ cell type (mesencymal, etc.) ○ But can differentiate, and include other cell types within themselves § Mixed tumor of parotid or salivary glands □ Duct-like structures - suggest epithelial components (containing mucin) (cancerous?) □ Fibroid like stroma § Firboadenoma □ Within the breast □ Fibrous structure (cancerous) and adenoma epithelial structure (stroma) • Parenchyma vs. stroma ○ Parenchyma: \_\_\_\_ cell ○ Stroma: surrounding \_\_\_\_ cells
divergent
cell
duct
stroma
cancer
supporting
Mixed tumor
Teratoma
____ and ____ cells or tissues from more than one ____ layer
Originate from ____ germ cells
• Teratoma ○ The original cell had the potential to develop into any type of germ cell § Totipotent germ cell (a stem cell) ○ Occurs during \_\_\_\_, but may not be noticed until later in life § Ovaries, etc., noticed due to \_\_\_\_ ○ Can be benign or malignant § Mature teratoma: \_\_\_\_ § Immature teratoma: \_\_\_\_ § If cell growth shows immature, it means it is more aggressive • Tooth, fat tissue, may be some muscle ○ All from different germ layers
mature
immature
germ
totipotent
development
mass effect
benign
malignant
• Kidney
○ Ectopically there are ____
○ An example of a teratoma
○ Cannot say whether it’s mature or immature at this level
teeth
Other Terms
Hamartoma
____ tissue mass within the tissue of ____
Choristoma
Normally ____ cells reflective of a tissue, but found in a distinct anatomic ____
• Hamartoma ○ Occurs in 70% of \_\_\_\_ tumors ○ See all components that make up lung tissue (alveolar walls, macrophages etc.), but not in usually architectural arrangement § Still in lung • Choristoma ○ Not in it's normal location ○ Someone cut off a piece of pancreas and put it in the colon
disorganized origin organized location lung benign
Feature Distinguishing Benign from Malignant
Well differentiated/Anaplastic
Rate of growth
Local ____
____
• Presence of only one doesn't mean that it is benign or malignant • If have local invasion or metastasis ○ Makes you feel most \_\_\_\_ that a tumor is malignant
invasion
metastasis
confident
Well Differentiated vs Anaplasia
Well differentiated Characteristic of \_\_\_\_ neoplasms Tissue organization is \_\_\_\_ \_\_\_\_ are rare Can occur in \_\_\_\_ tumors Retain tissue \_\_\_\_
Anaplasia Loss of cellular \_\_\_\_ Nuclei exhibit = \_\_\_\_ = hyperchromatism = \_\_\_\_ shape = nuclear to cytoplasmic ratio approaching \_\_\_\_ Numerous, atypical mitoses \_\_\_\_ tumor cells
• Anaplasia - complete lack of differentiation ○ Nuclei changes - one of these proves an anaplastic state § Pleomorphism: varying \_\_\_\_ of nuclei § Hyperchromatism: \_\_\_\_ nuclei; chromatin is condensed (a sign of a genetic problem) § Aberrant shape § Normal N:C ratio is \_\_\_\_ □ Nuclei is 1/5 of whole cell □ Cancer cells - huge nucleus
benign retained mitoses malignant function
polarity pleomorphism aberrant 1:1 giant
sizes
dark
1:5-6
• Anaplastic lesion on right: ○ Atypical \_\_\_\_ § Tripod nucleus (third arrow) □ \_\_\_\_ ○ Hyperchromatic nucleus ○ N:C approaching 1:1
• Well-differentiated lesion on left: ○ Glandular structures § \_\_\_\_ being produced (arrow) ○ Cells organized in parallel to each other ○ N:C is around \_\_\_\_
mitoses
tripod
mucin
1:5-6
Desmoplasia
Fibrous ____ associated with certain cancers
• Given to the name of the \_\_\_\_ that surrounding certain cancers ○ Not the parenchyma! • Neoplastic growth is supported by fibrous stroma ○ Common in \_\_\_\_ cancer • Gives a tough, rubbery appearance
stroma
stroma
breast
Dysplasia
Disorderly, but non- ____ proliferation
Largely occurs in ____ lesions
Loss of uniformity and tissue architecture
Mitoses are more abundant and not restricted to ____ layer
Mild to severe
Carcinoma in situ
Mild to moderate, may ____
• Well-diff and anaplasia help you distinguish between benign and malignant • Dysplasia: there's a change, but it's not necessarily anaplastic or a precursor to anaplastic changes ○ Consider it as pre-\_\_\_\_ in certain cases § Bronchial epithelium of tobacco smokers - if there is \_\_\_\_ and loss of \_\_\_\_ to an extent without mitotic changes it's called dysplasia ○ In most severe form - carcinoma in situ § Not cancer!
neoplastic
epithelial
basal
regress
neoplastic
cellular proliferation
cell organization
• Any change of epithelium that makes it disorderly is ____
○ Left: basal lamina separating the epi layer, basal cells that change to squamous
○ Right: there is cell proliferation, and disorganized
§ Dysplastic change
§ Not ____ yet!
dysplasia
neoplastic
Carcinoma in situ
• Carcinoma in situ: if in epi tissue contains the entire \_\_\_\_ of epi ○ Still contained within epi, and \_\_\_\_ is intact, but the structural loss affects the entire area ○ Debate whether or not it's cancer § If remove: cured most often than not; not considered a \_\_\_\_ process ○ Can see \_\_\_\_ figures in these lesions
thickness
basal lamina
malignant
mitotic
• Starts as a mild process and then progresses
○ Typical to lesions that exposed to inducers:
§ ____
§ UV light
§ ____ exposed via inhalation
• Left: normal
○ Basal lamina
• Next: if cells proliferate and look disorganized
○ Bottom ____: mild dysplastic change
○ If includes up to two ____: moderate dysplasia
○ If affects the all, and maybe sparing the top: ____ dysplasia
tobacco chemicals third thirds severe
• Bronchial epithelium
○ ____ epi
• Left: normal
• Next (B): epithelial appearance is lost and cells look more squamous
○ ____
○ Change in the morphology
○ Taking up one third of the total thickness of epithelium - mild
• Next (C): moderate dysplasia (two-thirds)
pseudostratified squamous
squamous metaplasia
• E: ____ dysplasia
○ At top there’s a line separating the squamous
• F: the entire thickness of epithelium looks abnormal
○ Includes the entire thickness: ____
• Carcinoma in situ = ____ dysplasia; if severe covers entire thickness of epithelium; but not all ____ dysplasia is carcinoma in situ
severe
carcinoma in situ
severe
severe
Rate of Growth
____ affects growth
New ____ can affect growth rate
Benign tumors grow more ____, but exceptions exist
In general, growth rate correlates inversely with ____ level in malignancy
• The less \_\_\_\_, the more likely it will be malignant ○ There are exceptions: § Some tumors of \_\_\_\_ grow slow, but they're highly invasive and malignant
blood flow
mutations
slowly
differentiation
differentiated
brain
Growth Rate, a Therapeutic Target: New Theories
Traditional therapies target ____ growth rate of tumor cells
Grow like ____ cells, with limitless capacity for division
Evidence that they arise from stem cells and precursor cells
– New theory of “tumor stem cells”
—- Resistant to therapies due to ____ growth rate
• Tumor stem cells ○ Grow slowly ○ They're not \_\_\_\_ stem cells, but have limitless capacity for division § If one left behind - can lead to another tumor § Have stem-cell like properties • Kill faster growing cells and now the ones left behind are these tumor stem cells ○ New therapies are being developed to target these special cells
faster
stem
slower
regular
Local invasion
Benign tumors Cannot \_\_\_\_ Remains localized at \_\_\_\_ Many are \_\_\_\_ Others have well demarcated \_\_\_\_
Malignant tumors Infiltrate into adjacent tissues Invade and destroy See microscopically at margins Next to \_\_\_\_, invasiveness most reliably distinguishes malignant from benign tumors
• Metastasis is the more reliable criteria to determine if a cancer is malignant; local invasion is the second best one ○ Benign can't invade because it's \_\_\_\_ • Can see \_\_\_\_ projections of invasion of malignant tumors under the microscope
invade
origin
encapsulated
borders
metastasis
encapsulated
finger-like
Metastasis
Secondary spread of tumor to distal tissues
Identifies a neoplasm as ____
Tumors differ in ability to metastasize
Brain (____) to bone (____)
Spread via: Seeding within body cavity Lymphatic -- Favored by \_\_\_\_ -- Identify \_\_\_\_ lymph node Hematogenous -- Favored by \_\_\_\_ -- Usually occurs in \_\_\_\_ -- Liver and \_\_\_\_ most frequent site
• Slightly different from local invasion - spread of tumor to distal tissue, not to neighboring tissue ○ Can be a lymph node or another organ • Regardless of size of tumor, some can metastasize very aggressively ○ Ostrocytoma - will remain in the brain? • Seeding within body cavity ○ More pertinent to tumors that grow inside an open cavity § Peritoneum □ \_\_\_\_ tumor - any tumor cell that is loosely attached and will spread throughout the peritoneum Tumor within the \_\_\_\_ that is close to ventricles, and a cell gets loose and develops in cavity; can grow anywhere the CSF goes to
malignant
low
high
adenocarcinomas
sentinel
sarcomas
veins
lungs
ovarian
brain
• Lymphatic (more common)
○ Adenocarcinomas - malignant tumors of ____ cell origin
§ Tumor uses lymphatic flow and seeds lymph nodes
§ Starts with nearest lymph node
○ Sentinel lymph node
§ In H+N cancers, the lymph nodes receive lymphatics depending on location
§ Based on location of tumor, you can predict which ____ is the likeliest to receive the tumor cell if spread
§ Dissect lymph nodes neighboring tumor and stain to check which ones are ____ (this is sentinel)
• Hematogenous (more common)
○ Sarcomas (bone, connective tissue, or muscle)
○ Veins - due to ____ flow that allows tumor to spread
§ Vena cava?
○ Liver and lungs more frequently involved because of the blood they receive
§ Liver from ____ cavity
§ Lungs from ____
○ ____ tumor can send cells through the veins and seed the liver
epithelial
lymph node
positive
slower
abdominal
head and chest
kidney
• Metastasis can be seen as tumor growth ○ Numerous • Left: liver ○ Different \_\_\_\_ metastatic lesions • Right: lung • Chest x-ray ○ \_\_\_\_ lesions
size
opaque
Epidemiologic snapshot 2010:
• ____ cancer related deaths are high among males/females
• ____ cancer is 3% of all cancers, causes death in 6% of patients
○ Death observation tells us it’s ____
• Tells us whether ____ or ____ factors are important in carcinogenesis
lung pancreatic aggressive age hereditary
Epidemiology
Major clues to cancer pathogenesis were uncovered by epidemiology Environmental -- \_\_\_\_ -- Occupational -- \_\_\_\_
Ethnicity (genetic, cultural) Heredity -- \_\_\_\_, AR, unknown Age -- Very \_\_\_\_ and very old Acquired pre-\_\_\_\_ lesions
• Environmental ○ Geographic studies § SE Asia chew things that develop cancer ○ Occupational studies § Inhalation of \_\_\_\_ leading to lung cancer ○ Behavioral studies § Lung cancer - \_\_\_\_ use □ More prominent in males, and then use increased in females • Ethnicity ○ Genetic - certain groups are more \_\_\_\_, and if mutation in population and it will remain and incidence will be higher ○ Cultural - Japanese is ethnic homogenous but culturally conserved population § \_\_\_\_ cancer is highly prevalent □ \_\_\_\_ and \_\_\_\_ are contributing factors • Age ○ Older people have accumulations of mutations ○ Very young (10% of children) can develop cancer § Because of \_\_\_\_ mutations that give rise • \_\_\_\_ can increase the risk of cancer ○ Bronchial epi in tobacco smokers - squamous \_\_\_\_ (pre-neoplastic change) ○ HPV increases the risk of \_\_\_\_ cancer ○ \_\_\_\_ in colon can be pre-neoplastic
geographic
behavioral
AD
young
neoplastic
benzene
tobacco
homogeneous
stomach
diet
genetics
germ-line dysplasia metaplasia cervical polyps
Environmental Factors
Most common cause of ____ cancer
e.g. UV sun exposure, tobacco consumption, alcohol consumption,
____, radon, vinyl chloride, ____, diet
“There is no escape: It seems that everything people do to earn a livelihood, to subsist, or to enjoy life turns out to be illegal, immoral, or fattening, or—most disturbing—possibly carcinogenic.”
* There is a \_\_\_\_ effect for most of these factors * Asbestos - no \_\_\_\_ effect - small exposure can lead to high increase in cancer risk * Cancer is genetic, but environmental factors play an important role in the majority
sporadic
asbestos
HPV
dose
dose
Epidemiology
Clues to diagnosis
May help with ____ or early detection via screening
E.g. ____ screening for cervical cancer, sunscreen, ____ cessation
prevention
HPV
smoking
• Benzene
○ Linked to ____
• Ni-compounds
○ ____ and lung cancers
• AD-cancer syndromes
○ Certain families are ____ to cancers
§ Inherit genes that are defective to start with, putting them at higher risk
§ Retinoblastoma - tumor of the eye, involves inactivation ____ of retinoblastoma
□ When an individual is born, if one gene has a mutation from germ-line and you have a defective and normal copy - in order for the tumor to occur both copies should be defective, so you’re now at higher risk comparing to someone with two normal copies
® ____: born with one allele genetically altered
§ P53 gene (tp53) - ____
□ Defective p53 copy, and if second is deleted or mutated > develop tumors in the GI tract
□ Can see within family that there are multiple individuals that develop cancers
○ Typically presented with characteristics that these patients are at higher risks for cancer
§ For AD retinoblastoma: happens ____
□ Inherited-cancer syndrome, and occurs ____ in life
§ If sporadic cancer, w/o defective copy: happens ____
Can say it penetrates in an ____ fashion
leukemia
nose
predisposed
TSG LOH Li-fraumony bilaterally earlier unilaterally AD
• AR-cancer syndromes
○ Involve genes that are important in DNA repair
§ ____ - the gene that is impt in DNA repair is mutated
○ Can say it penetrates in AR fashion
• Unknown inheritance
○ Certain families have breast cancer that occur more frequently, but cannot say whether it’s AR or AD
○ ____ cancer of certain types that are not linked to genetic changes in brca1/2 - they can run in families
§ In addition to ____ cancers
□ In ____ you have 2x the chance of getting ovarian cancer if one sibling has it
xeroderma pigmentosum
breast
ovarian
siblings
Proto-oncogenes
Cellular genes that induce uncontrolled ____ when mutated or overexpressed
Mutated or ____ forms are called oncogenes
Usually regulate cell division and survival
____ as mutation in a single allele leads to cellular transformation
• You're not losing function of this gene, the gene is gaining function ○ Normal functioning: proto-oncogenes ○ When mutated/duplicated: oncogenes
cell growth
overexpressed
dominant
\_\_\_\_ Receptors \_\_\_\_/GTPases/kinases Transcription factors \_\_\_\_ regulators Cell:cell, cell:matrix interactors
• Receptors that allow cell to interpret GF signaling that induces the cell to divide; or can be the ligand itself ○ Has to transmit the signal to the nucleus, which involves 2nd messengers, GTPases and kinases ○ Once to the nucleus, the TF needs to be turned on
ligands
2nd messengers
apoptotic
Tumor Suppressors
____ uncontrolled growth
Usually need mutation of both ____ for transformation
Governors (e.g. ____) stop cell ____
Guardians (e.g. ____) sense and regulate ____
— Lead to a ____ phenotype
• Guardians senses damage to DNA ○ Mutator phenotype - if p53 is mutated (both copies) there is no DNA repair, so that cell will become susceptible to accumulate more \_\_\_\_ damage or not respond to other mutations § Enables more \_\_\_\_ to occur • Require a mutation in both alleles for TSG in order for a cancer cell to transformation ○ Protooncogenes, all you need is one copy to be mutated for it to be active because it's \_\_\_\_
prevent alleles Rb p53 DNA repair mutator
DNA
mutations
Apoptosis and DNA damage
Regulators of ____ and ____ may behave as oncogenes or tumor suppressors.
• Cancer cells do not want to apoptose - will try to suppress apoptotic genes so that it will survive
apoptosis
DNA damage
Genetic Lesions in Cancer
Single base mutations
May be activating (e.g. ____ or EGFR)
May be inactivating (e.g. ____ or pRb)
Karyotypic changes \_\_\_\_ Deletions \_\_\_\_ Aneuploidy
* Can be a point mutation that changes AA and structure that is activating (PO) or inactivating (TSG) * Can have larger scale changes to karyotype
Ras
p53
translocations
amplifications
Balanced Translocations
Activates proto-oncogenes by:
Removing ____ elements
t(8; 14) removes the ____ regulatory elements and replaces with ____ – myc overexpression in 90% of ____
t(14;18) in 90% of ____; IgG promoter drives ____
• Translocation of regions from different chr that swap places • C-myc - protooncogene ○ Located on \_\_\_\_ ○ Heavy chain IgG that has regualtory element on \_\_\_\_, and this gets swapped in front of c-myc thereby makes it activated more easily ○ Still the \_\_\_\_ gene ○ If have Burkitt's lymphoma - genetic test and stain the chromosome ○ Proximity of chromosomes during cell division may increase the likelihood of this event occurring • \_\_\_\_ promoter after translocation is moved in front of Bcl-2 > increased expression
repressor
c-myc
heavy chain IgG
burkitt’s lymphoma
follicular B-cell lymphoma
Bcl-2
c8
c14
original
IgG
Balanced Translocation
Activates proto-oncogenes by:
Creating novel fusion protein
t(9;22) creates fusion between the ____ gene and the ____ oncogene
____ chromosome
• Translocation may result in a new gene • Bcr fuses with Abl oncogene - longer \_\_\_\_ ○ Hybrid gene - has higher \_\_\_\_ activity, that favors cell division
BCR ABL philadelphia c9 Tyr kinase
Deletions
Often associated with ____
Deletion of second allele with inherited mutation on other allele leads to ____
Deletion of ____, the site of the RB gene, are associated with retinoblastoma,
Deletion of ____ is associated with loss of TP53, Li Fraumeni syndrome
TSG’s
LOH
13q14
17p
Gene Amplifications
Homogeneous staining regions = \_\_\_\_ elsewhere in genome Generation of double minutes = \_\_\_\_ in 25-30% of neuroblastomas = \_\_\_\_ in 20% of breast cancer cases
• More observed with \_\_\_\_ ○ More gene product • Myc - protooncogene ○ If amplified during mitosis and multiple copies are made § It will stain as the same pattern ○ Number of copies varies, so length may be different • Her2/neu (ERBB2) - protooncogene • May form circular DNA fragments when stain chromosomes - double minutes ○ Can produce \_\_\_\_, but not part of the \_\_\_\_ • It's either one or the other: \_\_\_\_ or \_\_\_\_
duplication
N-myc
Her2/neu (ERBB2)
protooncogenes protein chromosome homogeneous double minute
Aneuploidy
Mistakes during mitosis are often observed in cancers
Mitotic ____ disruption, chromosomal ____
Proposed to cause cancer over 100 years ago…it clearly occurs during carcinogenesis but has not been established as cause
• No consensus on whether it induces carcinogenesis • In most cancers, the chromosome numbers are aneuploid (not \_\_\_\_) ○ Problem with check point that makes sure the chromosomes are separated evenly
check point
mis-segregation
46
MicroRNAs
Suppress mRNA ____ or induce mRNA ____
Contribute to carcinogenesis by:
= Decreased level of miRNA regulating ____
— ____, RAS in lung cancer and ____ in some lymphomas
= Increased levels of miRNA regulating ____
• miRNA ○ \_\_\_\_nt length gene products ○ Regulate at \_\_\_\_ level, not the genetic level
translation destruction oncogenes Myc Bcl2 22 mRNA
Epigenetics
____ and ____ modification regulate genome
Normally most of genome is ____ by modification
Cancer cells have global ____
= Increases genomic instability
Tumor suppressor genes are ____
= ____ and p16INK4a locus are hypermethylated in cancers
• Methylation - suppression ○ If hypomethylation an oncogene - there will be increased activity ○ If hypermethylation for TSG - decreased activity § P14 and p16 come from the same \_\_\_\_, but they're the protein products that are different
methylation histone modification repressed hypomethylation hypermethylated P14/ARF
gene
Epigenetics
Epigenetic state dependent on ____ type
= e.g. neuron vs keratinocytes
Different stimuli have different responses based on ____ baseline
= ____ stimulates pro-growth genes in T-cell context
= Notch 1 stimulates ____ functions (____) in keratinocyte context
• Although all cells have same genes, not all genes are active in all cells ○ Certain subsets active in neurons, but not in keratinocytes • [CUT OFF HERE]
cell epigenetic notch1 tumor suppressor p21
