Holistic Genes and Development Part 3

cytosines, CpG

In mammals, DNA methylation occurs at _____ in any context of the genome. However, more than 98% of DNA methylation occurs in a ____ dinucleotide context in somatic cells, while as much as a quarter of all methylation appears in a non-CpG context in embryonic stem cells (ESCs)

adenoma (some technically bignign, and others pre-malignant-talked about in another lecture)

Lineage: Epithelial, glandular What is it called if it is benign?

adenocarcinooma

Lineage: Epithelial, glandular What is it called if it is malignant?

Squamous papilloma, seborrheic keratosis

Lineage: Epithelial, squamos What is it called if it is benign?

squamos cell carcinoma

Lineage: Epithelial, squamos What is it called if it is malignant?

doesn't exist (binign hematopoietic, lmyphoid marginal zne B cell)

Lineage: Hematopoeitic, lymphoid, maraginal zone B cell. What is it called if it iis binign?

marginal zone lymphoma

Lineage: Hematopoeitic, lymphoid, maraginal zone B cell. What is it called if it is malignant

lipoma

Lineage: mesenchymal/adipose tissue What is it called if it is benign?

Liposarcoma

Lineage: mesenchymal/adipose tissue What is it called if it is malignant

melanocytic nevus (mole)

Lineage: neuroectodermal/malnocyte What is it called if it is begign?

melanoma

Lineage: neuroectodermal/malnocyte What is it called if it is malignant

mature teratoma (female)

Lineage:germ cell tumor: What is it called if it is begign?

mature teratoma

Lineage:germ cell tumor: What is it called if it is malignant?

hyperplasia (neoplasma is the clonal expnaion og genetically altered cells)

____ is not technically considered neoplasia because you still maintain the integrity of what you started with. If you started with 1Rred, blue and white cell, the proportions would be maintained, but they would just be present in larger numbers.

60, 40

__% of retinablastoma cases are sporadic, and __-% are genetic. In the latter, you get one allele from parents, and then, sometime during your life time, you get a mutation in the second. In the former case, you just lose both throughout your life.

oncogenes, tumor suppressors

_____ often cause senescene rather than proliferation. And ___ ___ apply the breaks to cell proliferation.

anaplasia

______ is a mophological correlate of neoplasia and refers to anything that involves the slowing of divisions/necrosis/apoptosis, etc.

NF1, NF2

___ and ___ are both tumor suppressors and we have learned about diseases caused when we mutate the two of them. The disease is called neurofibromatosis

benign, malignany

a ____ neoplasm tends to be less aggressive clinically, whereas a ____ neoplasm tends to be more aggressive

benign

a ____ tumor is localized, easily removed and typically associated with normal survival. Morphologically, it is similar to normal tissue and linked to low growth rate.

malignant

a ____ tumor: Invade and destroy tissue, may metastasize, typically associated with decreased survival especially if untreated. Some poorly differentiated tumors hard to classify. Broad range of morphologies but typically includes anaplasia. Highly variable growth rate.

low

a benigin tumor is localized easily removed and typically associated with normal survival. Morphologically, it is similar to normal tissue and linked to ____ growth rate.

less, more

a benign neoplasm tends to be ____ aggressive clinically, whereas a malignant neoplasm tends to be ____ aggressive

neoplasm

a clonal expansion os genetic altered cells.

anaplasia

a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells.

clonal

a neuplasm is defined as a _____ expansion of genetically altered cells.

epigenetic (these is a genetic change, but the root cause behind it is epigenetic)

Genetic or Epigenetic alteration? C) Decreased expression of mir-17-92 due to hypermethylation of its promoter

genetic (there is a epigenetic change, but the root cause behind it is genetic)

Genetic or Epigenetic alteration? D) MLL translocation leading to altered histone acetylation

Epigenetic (there is a genetic change, but the root cause behind it is epitgenetic)

Genetic or Epigenetic alteration? E) Altered histone acetylation leading to increased MYC

receptor

Growth factor, receptor, signal transducer or transcription factor: Which one is ERbb2?

growth factor

Growth factor, receptor, signal transducer or transcription factor: Which one is FGF?

transcription factor

Growth factor, receptor, signal transducer or transcription factor: Which one is myc?

signal transducer

Growth factor, receptor, signal transducer or transcription factor: Which one is ras?

genetic (there is an epigenetic change, but the root cause behind it is genetic)

Genetic or Epigenetic alteration? A) TET2 mutation leading to altered DNA methylation

Genetic (microRNA os getting upregulated, but the underlying thing is genetic)

Genetic or Epigenetic alteration? B) Amplification of the mir-17-92 locus

sporadic, genetic

60% of retinablastoma cases are ___, and 40% are ___. In the latter, you get one allele from parents, and then, sometime during your life time, you get a mutation in the second. In the former case, you just lose both throughout your life.

tumor suppressors

APC and TGF B are both common ___ ___ genes. Don't talk about this as much as we do about p53!

melanoma, colon, thyroid

B-raf is mutated in what three common cancers

D, 4, E, 2, A, 2, B, 1

Cyclin __/CDK_ works in the G1/S boundary, Cyclin __ and CDK __ works and helps the cel through the S phase. Cyclin __/CDK _ at the G2/S boundary, and Cyclin __/CDK_ working between G2/M.

non-contiguous

Metastasis: Secondary implants of a primary neoplasm at a location distant (___-______) from the site of origin.

histology

Most cancers today are diagnosed through what method?

ras, ra, map kinase

One of the hallmarks of cancer is sustaining proliferative signaling and one of the ways that cancer cells tend to do this is by up regulating receptors that bind to growth factors. This leads to increased growth. Another way to do it is to have an activating mutation in a protein within the growht pathway, which is the case in ____. In this case, downstream of the EGFR, you can have a constitutively active ____ that consistnetly activates the ___ ___ cascade.

30, 10, sub-clinical

a tumor is literally just a genetic, clonal expansion, and it takes about ____ divisions for us to clinically see it. And from there it just takes ____ more divisions to lead to death. Thus, much of the tumor's life tends to be ____-___ (we don't realize even the presence of the tumor)

transcription factors, myc

another way that we can sustain proliverative signaling, which is a hallmark of cancer, is to actually have a gain of function mutation in ___ ___, such as ___ (most popular one). This tends to translocate din burkitt lymphoma and amplified in breast/colon/lung and other cancers. This leads to enhanced self-renewal and blocks differentiation in cellular reprogramming to stem cell like states. This also activates many genes the promote proliferation, including cell cycle and metabolism genes.

tumor suppressors

aside frmo sustaining proliferative signalning, which is a hallmark of cancer, anotherhallmark is evading growth suppressors, and research into this lead to the discovery of what types of genes?

D, 2, A, 2, B, 1

cyclin ___/CDK_ help transition into the S phase, and then you have cyclin __ and CDK__ at the S/G2 boundry. Cylcin ___/CDK__ at the G2/M boundary.

mutation, accumulation

even though a tumor may start off with one particular ____, but by the time you see clinical representation, there may be a mass of different cells because of the ____ of mutations. This is why neoplasms tend to be associated with different types of mutations.

aggressivenes

even though we associate melignant tumors as being invovled in invading and destroying tissue, it is important to remember that there is a broad range of _____. Some lower grade ones might be described as begign and some might be be lower severity in general.

cancer

even though we have miRNA, histone changes and CpG methylation happening epigenetically, these markers are all changed in ____. The enzymes physically responsible for these processes get mutated.

FISH

for any cancer caused by a translocation, the test we often run is called _____ and we cna see if two different chromonal fragments overlap.

translocation, deletion, amplification, mutation

four things that can happen when you get genetic mishaps in a cancer cell: For example you can get ___ (where one part of chromsome can join another), ___ (where you lose the gene altogehter), ___ (you get an increase in the amount produced), and ____ (just a change in the genetic sequence).

apoptosis

if p53 can't repair all the dmage that is done it goes on to activate the ____ pathway because better to keep the damage to yourself than to affect toher cells.

Liquid

leukemias are things that we refer to as ____ tumors because they are in the blood.

new growth

literally means "new growth"

p53

most frequently mutataead gene in cancer.

epithelial, site, site

most tumors tends to be classified into the ____ family. And if that is the case, the the classification also depends on the ___, while ___ is not considered in classification of other tumors.

supportive (through hypomethylating agents to crrect some of the crappy transcription happening within the dysplastic cells), chemotherap, stem cell

myeloid malignancy: myelodysplastic snydrome: this is a clonal myeloid stem cell disorder, which means early on in the creation of stem cells, you have a mutation making it look dysplastic, and then every cell after that is the same. Furhtermore, this tends to result in macrocytic cells. The treatment for this tends to be _____ care, ____ to get rid of the crappy cells or ___ __ transplant (because recall that htis

p53, Rb

name a common tumor suppressor gene (name 2)

Myc, Ras, Abl

name three exmaples of oncogenes

proliferative signaling

one hallmark of cancer is sustaining ______ _____. This usually works through growth factor signal transduction cascades. The growth factors usually work in an autocrine or paracrine manner to act on the cell itself.

proliferative signaling, growth factors, activating

one hallmark of cancer is sustaining ______ _____.In this case, some cells will upregulate receptors that bind to ___ ___ and ultimately, that allows them to be more receptive to even the smallest signals. Sometimes, receptors will have ____ mutations so that you don't even need a growth factor bound and the ceill will keep dividing.

retinoblastoma

one of the protoypical tumor supressor genes, and the one associated with the two hit hypothesis, which is associated with the loss of heterozygosity.

DNA

one of the ways that we inactivate p53 is by mutation in its ___ binding domain so that it can no long transcribe all the genes it needs to regulate the genome.

transcription factor, p21, DNA, apoptosis

p53 is a ____ ____ for VARIOUS proteins and is especially important beacuse it is activated in response to ANYTHING BAD THAT HAPPENS TO THE GENOME. This includes the protein ___, wihch can go and inhibit various Cyclin/CDK complex, and also stimulating ____ repair. And if all else fails p53 can also stimulate ____ of the cell.

E2F, D, 4, E2F

reintablastom works because it binds to ____, and when it binds to it, the cell cannot enter the ___ phase. However, when the Cyclin__/CDK __ (working at the G1 S boundary) is around, it will phosphorylate the Rb, and lead to releasing ___.

S, p16

retinablastoma works by binding E2F, and while it is bound, it can't go intot he nucleus and sitmulate the __ phase. However, when there is the CDK4/Cyclic D complex, it will phosphorlayate Rb and let E2F go. However, know that if there is DNA damage, the Cyclic/CDK complex in this step is inhibited by ___.

metastasis

secondary implants of a primary neoplasm at a location distant from the site of origin

Fibroadenoma

solid, noncancerous breast lumps that occur most often in women between the ages of 15 and 35

Gap, Raf

some cancers have mutations in Ras, but other cancers also have mtuation in ___ , which helps with the hydrolysis of the GTP bound Ras and in ____, which needs to be bound to Ras to start the map kinase cascade.

oncogenes

sustaining proliferative signaling is the hall mark f cancer, and researching this lead to teh discovery of ___

false (causes production of proteins that usually half the cell cycle)

t/f: A) p53 is a transcription factor that causes production of proteins that stimulate the cell cycle

true

t/f: p53 prevents the replication of cells with damaged DNA

fatty, red

the breast is made up mostly of ______ tissue, and it tends to sit on muscle, which tends to be ____ in color

p53

the guardian of the genome is what?

malignant

the number one difference between benign and malignant tumors is the the ____ tends to invade and destroy tissue

invade, destroy

the number one thing about malignant tumors is that they tend to ___ and ____ tissue.

histones, methylation, DNA, repression, miRNA, dicer

there are three main types of epigenetic changes: first is changes to the ____, which can come in the form of acetylation, methylation. You can have ____ of ____ - particularly at CpG sites, and that leads to ____ of those sites. Lastly, you can have ____, which are short pieces of RNAs that are processed through an enzyme called ___ that have complementarity to mRNAs and often prevent their translation,

K, H, N,15-20% (humans tumors that contain a mutated Ras)

there are three types of ras: what are they? And they are mutated in what percent of human tumors?

MDM2, MDMX

there is a protein called ____ and ___ that usually binds to p53 and degrades it. This is usually wher ep53 is bound if nothing is going wrong. Cancers have learned to take advantage of this and upregulate/promote this binding so that p53 can't induce repair.

DNA, p21, p16

there is a syndrome (Li Fraumeni) wher eyou inherited on e mutated p53 molecule, and that increases your chances of developing a malignant tumor by the time that you are 50 by 25% . Recall that p53 will sense ____ damage, and ultimately activate downstream factors like ___ and ___ to ultimately inhibit various cyclic CDK complexes until the damage is restored.

Li Fraumeni

there is a syndrome ___ _____ snydrome ) wher eyou inherited on e mutated p53 molecule, and that increases your chances of developing a malignant tumor by the time that you are 50 by 25% . Recall that p53 will sense DNA damage, and ultimately activate downstream factors like p21 to ultimately inhibit various cyclic CDK complexes until the damage is restored.

Tumor grade

this is a morphological insight into how bad a tumor really is. Well differentiated cells are more similar to non-neoplastic cells, but you also need to take into acount the heterogeneity of cells that you see.

lung

to diagnose neoplasias, we also do a ton of molecular testing. For one thing, EGFR tends to eb mutated in ____ cnacer

colon and pancreatic cancer.

to diagnose neoplasias, we also do a ton of molecular testing. For one thing, K-ras tends to eb mutated in ____ and ____ cancer.

K-ras

to diagnose neoplasias, we also do a ton of molecular testing. For one thing, ___-____ tends to eb mutated in colon and pancreatic cancer.

EGFR

to diagnose neoplasias, we also do a ton of molecular testing. For one thing, ____ tends to eb mutated in lung cnacer

EGFR

to diagnose neoplasias, we also do a ton of molecular testing. For one thing, _____tends to eb mutated in melanoma, colon and throid.

chemotherapy, efflux, uptake, inactivate, active

tumor cells can also get acquired resistance, and this happens once the cancer sees the ___. The cancer can evolve to get the drug out of its body through drug ___, it can learn to ultimately ____ less of the drug, it can learn to ____ the drug altogether, and it can even decrease the conversion of the drug into its ____ forms.

immunohistochemistry

tumors are often defined by their lineage, and so we often tend to have______ for certain proteins linked to the fate of certain cells to identify them.

immunohistochemistry

tumors are often defined by their lineage, and so we often tend to have______ for certain proteins linked to the fate of certain cells to identify them. For example, they did this with keratin to identify epithelial cells.

cell (name the cell frmo the site at which the tumor arose)

usually when we see a tumor cell, it usually retains information of the cell that it came from, and when it does, we try to name it based on the ___ that it resembles.

lineage, molecular

we classify neoplasms through the cell ____ and sometimes through the ______ markers they express.

age

we tend to describe a tumor by the stage it's in and this is a proxy for the ___ of the tumor in a way.

B-raf

what tends to be the common mutation in melanoma, colon and thyroid cancer?

leukemia

what would a liquid tumor be called?