4. Cancer I Flashcards by J L

• ____ 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

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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

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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

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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

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• 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

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• 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

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• 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

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• 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

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• Benign tumor pathology
○ ____
○ These examples are colon polyps
○ Well structured and ____

capsules

bordered

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Malignant tumors

	• The edge is not \_\_\_\_
	• Middle: malignant melanoma
		○ \_\_\_\_ borders
	• Right: malignant melanoma
		○ Scar tissue on the top

clear

irregular

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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

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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

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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

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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

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• Kidney
○ Ectopically there are ____
○ An example of a teratoma
○ Cannot say whether it’s mature or immature at this level

teeth

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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

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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

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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

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• 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

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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

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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!

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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!

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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

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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

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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 ```

4. Cancer I Flashcards

(51 cards)