Cancer BIO Exam 1 Flashcards
As mutations happen during cell divisions, More cell divisions lead to
More chances of DNA fidelity (replication) errors
Research: increased usage of tobacco (smoking) can lead to
Increased chances of getting cancer (lung)
Somatic DNA changes
-Happens in non reproductive cells of an individual
- acquired/present in single cell
-cannot be inherited
-can lead to cancer
Germline DNA changes
-present in all cell of individual including sperm and egg
-can increase susceptibility to cancer
-can be inherited
Autosomal dominant
One copy of gene from either parent is enough to present/ express the trait
Autosomal recessive
Two copies from one and the other parent to present/ express the trait ( meaning both parents must have the gene)
variable penetrance
(refers to the proportion of individuals carrying a specific genetic variation (allele) associated with a trait or condition who actually express the trait or develop the condition)
the cancer gene is present in the person, but it doesn’t mean the person will have cancer
variable expressivity
(The expression of the genetic trait can vary among individuals carrying the same genetic alteration.)
is when a cancer gene is present, but expresses itself differently.
ex: brca gene can be present in two people, but can manifest as ovarian cancer for one, and breast cancer for the other
common variants (low penetrance
individuals carrying a specific genetic variation associated with a risk of developing cancer may not necessarily go on to develop the disease
ex:
even if someone has the gene linked to cancer, their likelihood of actually developing cancer is relatively lower compared to individuals with a higher penetrance
rare variants (moderate penetrance) gene variants like BRCA 1 & BRCA 2
individuals with this genetic variation have a higher risk of developing cancer compared to those without the mutation, but the association is not absolute
rare variants (high penetrance) gene variants like BRCA 1 & BRCA 2
if an individual carries a specific genetic mutation associated with cancer, there is a high likelihood that they will develop the associated cancer
ex:
individuals carrying that mutation are at a significantly increased risk of developing breast cancer compared to those without the mutation
The chance of getting cancer increase when mutations in these genes (brca 1 and 2) happen. Why?
BRCA 1 and BRCA 2 are DNA repair enzymes. If mutation happens— that means there is less Dna repair, more Dna damage (leading to cancer)
what causes cancer?
-hereditary (lowest chance): inherited genes passed by parents to child
-familial (mid-chance): genes with lifestyle and environment
-sporadic (highest chance): happens by chance from somatic mutations
Primary site like:
1. Breast
2. Skin
3. Lung
4. Prostate
5. Colon
6. Pancreas
… and many, many more … is the?
The organ location in the body where the cancer first developed.
Histological type: Tissue type of origin, which groups hundreds of types of cancer into six general categories:
1. Carcinoma-in epithelial cells like skin, body cavities, organs
2. Sarcoma- in bones and soft tissues
3. Myeloma-in plasma cells
4. Leukemia-blood cells which stem from bone marrow
5. Lymphoma- in immune system like lymph nodes, spleen, stomach, testicles
6. Mixed Types-other cell/tissue types
carcinoma
- most common (80-90% of cancer)
*malignant neoplasm of epithelial origin (means cancer of internal or external lining of the body) - affects organs and glands responsible for secretion like breasts, lungs,, colon, prostate, bladder
subtypes of carcinoma:
*adenocarcinoma–Originates in an organorgland, and generally occurs inmucusmembranes. They often spread easily through thesoft tissuewhere they occur.
*squamous cell carcinoma–Originates in the squamousepithelium, many areas of the body.
Leukemia, Lymphoma, and Myeloma
White blood cells (WBCs) accumulate in the bloodstream.
Depending on the subtype, WBCs can also accumulate in the spleen or lymph nodes
Key Types of Leukemia:
Acute Myeloid (or Myelogenous) Leukemia (AML)
Chronic Myeloid (or Myelogenous) Leukemia (CML)
T-cell Acute Lymphocytic (or Lymphoblastic) Leukemia (T-ALL)
B-cell Acute Lymphocytic (or Lymphoblastic) Leukemia (B-ALL)
Chronic lymphocytic leukemia (CLL)
More subtypes….
Key Types of Lymphoma:
Non-Hodgkin’s Lymphoma (NHL)
Diffuse Large B-cell Lymphoma (DLBCL)
More subtypes….
Key Types of Myeloma
Multiple myeloma
More subtypes…
signs of cancer:
*A palpable lump under the skin can be either the tumor itself or a swollen lymph node
*see google notes
*mammography-screening for breast cancers
*Prostate Specific Antigen (PSA) screening for prostate cancers
**prostate gland releases PSA molecules in blood (low PSA levels are normal, but high PSA levels can be a sign of prostate cancer–but it could also be just UTI, rigorous exercise, ejaculation, enlarged prostate)
*Pap smears can detect abnormal cells from the cervix and are recommended every 3 years.
*Human papilloma virus (HPV) is a primary cause of the majority of cervical cancers.
*However, HPV is considered as a risk factor and many women with HPV never develop cervical cancer.
*HPV is a common sexually transmitted disease whose risk can be mitigated by prophylactics.
*The risk of transmission can be mitigated by HPV vaccines. Both men and women can be vaccinated against HPV to decrease spread. The CDC recommends HPV vaccines for people ages 9-15.
Benign nevus (mole) or melanoma. How do we know it’s melanoma?
Check for:
*Asymmetry-the two halves of mole look different
* Border-is poorly defined or irregular
*Color- varies from one area to another
*Diameter-bigger than a pencil eraser
Colonoscopy to screen for colorectal cancer
Colonoscopies are recommended every 10 years for people age 45 to 75 by the U.S. Preventative Services Tas Force
A tumor biopsy
is a procedure where a sample of tissue is taken from a suspicious mass or lump to examine it for the presence of abnormal cells. It helps diagnose and determine the nature of the tumor.
H&E stain, or Hematoxylin and Eosin stain
, is a common histological staining technique used in pathology. Hematoxylin stains cell nuclei blue, while Eosin stains cytoplasm and extracellular matrix pink, providing contrast and helping to visualize tissue structures under a microscope (to see if theres abnormal cell growth and loss of tissue organization)
Immunohistochemistry (IHC)
is a technique used in pathology to detect and visualize specific proteins in tissue samples. It involves using antibodies that bind to the target proteins, followed by a chemical reaction that produces a visible stain. IHC is valuable in identifying specific markers associated with various diseases, including cancer. It provides additional information about the protein expression patterns within tissues, aiding in diagnosis and understanding the biological behavior of diseases.
- IHC is very flexible because the primary antibody can be against any cell surface marker (that someone has made a good antibody against)-meaning it wont detect non cancerous cells
Positron Emission Tomography (PET) scan
PET scans use a slightly radioactive tracer to identify internal regions that have unusual metabolism, can pick up cancer very early
*if there’s an increased metabolism in certain area which usually doesn’t have organ positioned there or even with normal organ that has abnormal metabolic activity, it may reveal a possible cancer cells because cancer cells have high metabolism
Flow cytometry
*flow cytometry can indicate the presence of cancer when specific immune markers on cells glow brightly. Abnormalities in the expression of surface markers, such as CD antigens, can be detected through increased fluorescence during flow cytometry analysis. These changes may suggest the presence of cancerous cells or abnormal immune cell populations.
* a patient’s blood sample is stained with fluorescently labeled antibodies targeting specific immune cell markers. The fluorescence patterns generated when these antibodies bind to their respective markers help identify and characterize different immune cell populations, including cancerous or abnormal cells.
Liquid biopsy
is a non-invasive diagnostic technique that involves analyzing components of bodily fluids, such as blood, to detect and monitor various conditions, including cancer.
* often used when there’s a suspicion of cancer but obtaining a tissue biopsy may be challenging or invasive
1.Blood Sample Collection: A blood sample is taken from the patient.
Isolation of CTCs: 2.CTCs shed from tumors into the bloodstream are isolated from the blood sample.
3.Analysis of CTCs: The isolated CTCs are then analyzed to provide information about the cancer, such as its type, genetic mutations, and potential for metastasis.
Cancer onset can be slow
Stages of breast cancer
Stage 0: ductal carcinoma in situ
Stage I: Small, invasive, has not spread Stage IIA: ≤20 mm and 1-3 lymph nodes or ≤50 mm
Stage IIB: 20-50 mm and 1-3 LN or >50 mm without spread to LN
Stage IIIA: Spread to 4-9 LN or >50 mm with 1-3 LN
Stage IIIB: Spread to the chest wall or caused swelling or ulceration of the breast, or it is diagnosed as inflammatory breast cancer
Stage IIIC: Spread to 10+ LN but nowhere else
Stage IV (metastatic): Spread to other organs
HER2 (positive and Negative)
HER 2 positive means:
-overexpression of HER2 protein (increased number)
-cancer is more aggressive–more growth of cancer cells
-targeted therapies may work
HER2 negative means:
-no overexpression of HER2 protein
-targeted therapies may not work
ER (positve and negative)
ER+: cancer grow because receptor are present that binds to estrogen.
-also means therapies can be used for this type
ER-: no receptor present
-therapies that work to inhibit cancer growth may not work because of no presence of receptor
PR (+ and -)
PR+:may respond to hormonal therapies because of the presence of receptors that may be inhibited
PR-: hormonal therapies may not work
Rank greatest prognosis to worst prognosis (1-8, 8 as the worst)
1.HER2-,ER+,PR+
2. TRIPLE POSITIVE
3.HER+,ER-,PR+
4.HER2+,ER+, PR-
5.HER2+,ER-,PR-
6.HER2-,ER+,PR-
7.HER2-,ER-,PR+
8. TRIPLE NEGATIVE
Metastasis Process
- Primary tumor formation (still in tissue or organ)
- Local invasion (break off from boundaries of organ/tissue)
- Intravasion (cancer cells have invaded/entered the circulatory system/blood vessels)
- Survival in the circulation (cancer cells continue to travel through blood/lymphatic vessels- possibly successful in evading immune system response)
- Arrest at a distant organ site (cancer cells may not immediately start growing and forming tumors. Instead, they might enter a phase of dormancy or latency,”lingering” at the new organ without actively invading or forming detectable tumors. This period of arrest allows the cancer cells to adapt to the new microenvironment and conditions in the distant organ before resuming growth and colonization)
- extravasation (cancer cells escape from blood vessels or lymphatic vessels and invade the surrounding tissues)
- micrometastasis formation (established in a new location, these cancer cells can start to grow and divide)
- metastatic colonization (more advanced stage where these cancer cells have successfully established themselves- proliferated in the new site)
- clinically detectable macroscopic metastases (presence of secondary tumors that have grown to a size that can be visually identified or detected through clinical examination, imaging techniques, or other diagnostic methods)
COMMON ROUTES OF METASTASES
*STARTS IN BREAST-CAN GO TO liver,lung, bone, brain
*starts in colon-can go to lungs, liver
* from stomach- to esophagus, liver
*from lung- to adrenal gland, brain, liver
* from pancreas- to lung, liver
* from prostate-to bone
progression to colon cancer
benign:
1. hyperproliferation
2. small adenomatous polyps
3. large adenomatous polyps
4. severe dysplasia (precancerous polyp)
malignant:
5. adenocarcinoma
6. cancer
stages of colon cancer
- cancer cells only found in innermost lining of the colon (hasn’t spread)
I.tumor has spread beyond the inner layer but remains in colon
II. cancer has grown outside the colon, but not yet spread to lymph nodes
III. cancer has grown outside the colon, has spread to lymph nodes
IV. cancer has spread to other parts of the body
Rate of progression of colon cancer with or without surgery
*greatest progression of cancer–without surgery
*least–with surgery
lung cancer
Small-cell lung cancer (SCLC):
-typically initiates in the bronchii
-more tightly associated with smoking
Subtypes include:
-Small cell carcinoma
-Combined small cell carcinoma (mixed SCLC and NSCLC)
Non-small cell lung cancer (NSCLC):
-cells lining the surface of the lung airways. These include the bronchi, bronchioles, and alveoli.
Subtypes include:
1. Adenocarcinoma in situ
2. Adenocarcinoma (begins in glands in the alveoli, slow-growing, most common)
3. Squamous cell carcinoma (second most common overall, most common in smokers, begins in squamous cells, slow-growing)
4. Large cell (undifferentiated) carcinoma (least common, begins in large cells in lungs, fast growing)
lung cancer progression
Stage 0 – the tumor hasn’t grown outside of the lungs and is also called “in situ” disease.
Stage IA: tumors are ≤ 3 cm, no spreading to lymph nodes
Stage IB: tumors are 3-4 cm, no spreading to lymph nodes
Stage IIA: 4-5 cm, no spreading to lymph nodes
Stage IIB: 4-5 cm, spread to lymph nodes
Stage III: Spread outside of the lung to nearby structures including lymph nodes, but not to distant parts of the body.
Stage IV: Metastatic spread to more than 1 area in the other lung, the fluid surrounding the lung or the heart, or distant parts of the body through the bloodstream.
prostate cancer stages
Stage I:Slow growing, low PSA, cannot be felt and involves ≤ one-half of 1 side of the prostate. The cancer cells look like healthy cells.
Stage II:PSA medium or low, no spreading.
Stage III:PSA levels are high, the tumor is growing, or the cancer is high grade. These all indicate a locally advanced cancer that is likely to grow and spread.
Stage IV:The cancer has spread beyond the prostate.
stages of pancreatic cancer
Stage 0: Carcinoma in situ
Stage IA: ≤2 cm, no spreading
Stage IB: ≤ 4 cm, no spreading
Stage IIA: >4 cm, no spreading
Stage IIB: Any size, spread to ≤3 nearby lymph nodes but no distant sites
Stage III: Any size, spread to 4+ nearby lymph nodes OR nearby blood vessels, but no distant sites
Stage IV: Tumor is any size and has spread to distant sites
pancreatic cancer Pathological tumor grades
Pathological tumor grades:
-Grade 1 (G1) means the cancer looks much like normal pancreas tissue.
-Grade 2 (G2) falls somewhere in between.
-Grade 3 (G3) means the cancer looks very abnormal.
stages of melanoma
0: melanoma confined to epidermal region of skin
I:localized disease, only in skin but very thin
II:localized disease, thicker than stage I
III:spread to lymph nodes
IV:spread to other organs
stages of brain tumors:
I: slow growing cells, almost normal appearance, least malignant, usually long-term survival
II: relatively slow growing cells, slightly abnormal appearance, can invade nearby tissues, sometimes recur as higher grade
III: abnormal cells proliferation, abnormal appearance, infiltrate normal tissue, recur as a higher grade
IV:rapidly reproducing abnormal cells, very abnormal appearance, area of necrosis in center, angiogenesis
Peyton Rous
Can the cancer be transmitted without the cancer cells being injected
Rous Sarcoma Virous
Carcinoma from one chicken was isolated, grind up, and injdcted into another chicken. Observed was the chicken who got the carcinoma developed cancer.
Conclusion: cancer can be caused by virus (virus containing oncogene)
Focus forming assay
Used to identify oncogene
Injected cancer DNA to normal cell in the petri dish, then Analyzed the foci developed when cancer cells transformed the cell in dish, and analyzed even more which gene caused the transformation
Where does the cancer-causing part of tumor viruses come from?
Experiment by J Michael Bishop and Harold Varmus
1975 Experiment: Compared Rous Sarcoma Virus genome vs. non-foci forming variant to identify the cancer-causing gene. ( i assume the cancer causing agent was from rsv genome)
Then they compared the cancer-causing gene to animal genomes.
Result: The gene in the virus that caused cancer matched a nearly identical gene in animal cells! ( meaning that normal cells have the same gene, but only mutated in cancer cells)
Retrovirus can inject its genetic material into us( host cell),
Recombination event can alter retrovirus into an oncogneic retrovirus
Once the oncogenic retrovirus inject its genetic material into or near the protooncogene of the host cell, it can activate the host cell’s gene to become oncogene(increased proliferation of normal cells)
Retrovirus can pick up cancer causing genes inside one host cell and transmit it into another host cell
C src (cancer causing gene present in the normal cell)
V src (dsDNA provirus from avian leukemia virus + C src)
How does C src turn into V src
A harmless virion (avian leukemia,virus),
through infection and reverse transcription, creates dsDNA provirus. When dsDNA provirus gene is accidentally injected in the host cell DNA near C src gene and enclosed in capsid, the RSV now contains mutated gene of src gene-which js an oncogene)
Protooncogenes
Proto-oncogenes are a group of genes that cause normal cells to become cancerous when they are mutated
Oncogene
Mutated protooncogene that causes an increased proliferation of normal cell( now abnormal)
So can virus really cause cancer?
Tumor promoting virus were important in the discovery that cancer are caused by mutation in protooncogene which result in oncogene
Homolog
- Homologs:
derived from a common ancestor gene through speciation
A. Paralogs:
genes within the
same species that have arisen through gene duplication events
Ortholog
B. Orthologs: genes found in different species that evolved from a common ancestral gene through speciation
(genes which evolved from a common ancestral gene by speciation)
Analog
- Analogs: Genes with a similar function that do not share a common ancestor, resulting from convergent evolution (structures or traits are those that have similar functions or purposes but evolved independently in different lineages and do not share a common evolutionary origin)
Coding mutation in protooncogene results in
Why?
Abnormal protein
changes in the DNA sequence of the gene affect the amino acid sequence of the protein it encodes. These mutations can include substitutions, insertions, deletions, or rearrangements of nucleotides within the gene. altered amino acid sequence of the protein, can lead to changes in its structure, stability, or function
Regulatory mutation in protooncogene results in
How?
Excessive amount of protein
occur in regulatory regions of the gene, such as promoters or enhancers, or in transcription factor binding sites. These mutations can alter the normal regulation of gene expression, leading to increased transcription of the proto-oncogene and ultimately higher levels of the corresponding protein.
Translocation in protooncogene results in
How?
Novel protein
The protooncogene becomes fused with another gene, transcribed and translated. The resulting fusion protein may have abnormal activity compared to the original protein. Then that promotes abnormal activity
Gene amplification iof protooncogene results in
How?
Excessive amount of protein
multiple copies of the gene are present within the cell. So, there is an increased abundance of mRNA transcripts derived from the amplified gene, which are then translated into protein by the cellular machinery. With more copies of the proto-oncogene being transcribed and translated, the production of its corresponding protein is elevated.
Point mutations in coding regions
Silent- a change in both DNA and mRNA level, but the translated amino acid sequence isn’t affected so the mutation had no effect
Nonsense-introduce a premature stop codon into the coding sequence
Missense (conservative): does not completely alter the function of the amino acid. substituted amino acid has similar chemical properties to the original amino acid
Missense (nonconservative):
the substituted amino acid has different chemical properties from the original amino acid. may significantly alter the structure or function of the resulting protein.
Point mutations in (blank) drive 15-30% of all cancers
How?
KRAS
Point mutations in the KRAS gene can lead to constitutive activation of the KRAS protein, meaning that it remains in its active GTP-bound state even in the absence of upstream signaling stimuli
RAS isoforms are:
KRAS, HRAS, NRAS
P-loop:
Switch I:
Switch II:
( G domain contains P-loop): which forms part of the nucleotide-binding site. (Where GDP and GTP binds to)
Effector lobe: interacts with downstream effector proteins, transmitting signals from activated Ras to intracellular signaling pathways.
Switch I:undergoes conformational changes upon nucleotide binding. (GDP bound means closed conformation, while GTP bound means open conformation- means ras is activated)- also more focused on exposing the binding site of p loop
Switch II: undegoes the same conformational changes, but it is more invovled in stabilizing the binding between ras and nucleotides
Hypervariable region HVR contributes to the diversity of Ras isoforms.
Even when switch i and switch ii are disruoted, as long as the p loop is able to bind gtp, ras activation can still happen. Not in its full extent capacity, but ras activation can still help in progression of cancer
Recurring RAS point mutation in cancer
What amino acid gets mutated at position 12 of the sequence that results in uncontrolled cell growth-leading to cancer
glycine is replaced with valine
KRAS cycles between “on” and “off” states
(RTK, GTP, GDP, RASGEF, RBD, KRAS)
steps:
- When a ligand binds to a receptor tyrosine kinase (RTK), it triggers a signaling cascade that ultimately leads to the activation of RAS proteins like KRAS. RTK recruits RASGEF.
- RASGEF like SOS promote the exchange of GDP to GTP (for activation “on”)
- GAPs like NF1 and P120 RASGAP stimulate GTPase activity of KRAS (which is responsible for hydrolysis of bound GTP to GDP-inactivation), as GTP is hydrolyzed into GDP, an inorganic phosphate is released.
- when active GTP is bound to KRAS, effectors like RAF and P13K kinases bind to RBD to enhance proliferation and growth
what happens when there’s a mutation in codon 12 and codon 61? what is likely the result of this mutation?
- Mutations in codons 12, 13 and 61 disrupt the GTP hydrolysis and guanine exchange rates of RAS proteins
- mutations in codon 12 disrupt the GTPase activity of RAS —which decreases the rate of GTP hydrolysis, so the mutant protein accumulates in the GTP-bound state (increased activation)
- Mutations in codon 61 accelerate the rate of GDP–GTP exchange and simultaneously decrease the rate of GTP hydrolysis, so codon 61 RAS mutants also accumulate in the GTP-bound state (increased activation)
***Mutations in codons 12 and 61 of the RAS gene are associated with decreased GTP hydrolysis activity. So, RAS proteins with these mutations tend to remain in the active (GTP-bound) state for longer periods of time. REsult: prolonged activation of downstream signaling pathways involved in cell proliferation, survival, and differentiation contribute to the development and progression of various types of cancers.
how can Alterations in noncoding regions of the genome cause oncogenesis?
enhancers: DNA sequences that increases transcription of genes (help regulate which genes gets turned on or off)-like bookmarking which pages needs to transcribe
Cohesin and CTCF: help organize chromatin structure and regulate gene expression (create loops to make dna accessible)—book page holder make it easier to copy pages
RNAPII: responsible for transcribing DNA into RNA during the process of gene expression— the real transcriber
Transcription factors: regulate the transcription of genes (ensure that the copying is right)— like the person double checking the info
**if something goes wrong with the way genes are being copied or there’s too much genes being copied, that leads to cells growing incorrectly and wrongly which leads to cancer
Mechanisms of genomic amplifications (extra copies) of an oncogene in cancer:
- double minutes–extrachromosomal fragments of DNA that contain amplified sequences like oncogenes. They replicate independently. Can arise through errors and chromosomal breakage
*Homogeneously Staining Regions (HSR)–appear as intensely stained bands due to high DNA amplification. Amplification can happen due to unequal crossover events during meiosis
*scattered–extra copies of oncogene are dispersed across multiple chromosomes rather than being concentrated in specific regions
***genomic amplifications of oncogenes play a significant role in driving cancer progression by increasing the expression levels of genes that promote abnormal cell growth and survival.
N-myc in neuroblastoma
which mechanism of amplification is it associated?
This amplification is associated with the formation of either double minutes (DMs) or homogeneously staining regions (HSRs)
- The HSRs, which contain multiple copies of the genomic region encompassing the N-myc gene
*often have low prognosis
How many copies of each gene?
identify using Array Complete Genomic Hybridization (aCGH)
steps:
- label differently the tumor and reference (normal) DNA sequence
- add unlabeled blocking DNA to prevent repetitive DNA sequence
- all three components are added together and hybridized into a microarray containing millions of DNA probes of the entire genome.
result: the ratio of fluorescent signals will be the same if there is no difference between the tumor and reference sequence.
If the ratio is altered, that means there must be amplification or deletion that happened in the tumor sequence, which can help identify the genomic location of the genes that undergone amplification/deletion
Mechanisms of gene amplification and rearrangement
- normal crossing over–genes are on their normal lines, with no rearrangement, and getting amplified normally
- genes do not match (one gene gets behind, so the other gene gets lined up with a different gene)
result: either complete gene duplication happens (normal genes still together) or crossing over results with partial gene duplication (abnormal gene)—gene rearrangement
How is the Amplification of extrachromosomal double minutes harmful?
Double minutes are replicated during S phase to form paired structures. In mitosis, double minutes attach to chromosomes at metaphase and are found in proximity of the chromosome tips in anaphase. Sister double minutes remain paired during G2 and mitosis, and their mitotic nondisjunction results in unequal distribution of double minutes over daughter cells
Double minutes aren’t connected
to spindle fiber machinery, so
copies are distributed randomly.
After mitosis these two daughter
cells could have received 0-8
copies, leading to fast genomic
amplifications and deletions.
conclusion: double minutes undergo replication and distribution during the cell cycle in a manner that is independent of the cell’s normal chromosomal machinery—this leads to random/rapid distribution of genes–contribute to cancer
ways cell may create a double minute (circular DNA)
a)replication>re-replication> DSB formation> circularization
b) replication> DSB fformation> circularization > continued replication
c) DSB formation> circularization> homologous recombination
d)DSB formation> circularization> non-homologous end joining
How can translocation activate oncogenes?
translocation– fuse a region from one chromosome with a region from a second, unrelated chromosome
***When the c-myc gene ends up next to IgH, it starts following the rules of IgH, which tell it to grow a lot all the time. This makes the c-myc gene produce too much of a protein called Myc, which tells cells to grow really fast. This extra growth can cause Burkitt’s lymphoma.
Myc translocations cause ~70% of Burkitt’s lymphoma cases
(through reciprocal translocation—myc protooncogene becomes myc oncogene)
The aberrant expression of the c-myc oncogene leads to the production of structurally normal Myc protein but in abnormally high amounts.
can Oncogenic amplification of HER2/Neu lead to a worse prognosis after being diagnosed with breast cancer?
it suggests that the presence of amplified erbB2/HER2 gene and elevated protein expression correlates with a more aggressive form of breast cancer and poorer prognosis compared to cases where the gene is not amplified and protein expression is normal
which chromosomal translocation cause fusion protein?
Reciprocal chromosomal
translocations between human
Chromosomes 9 and 22, which carry the abl and bcr genes (BCR-ABL translocations) turn out to be the single cause of virtually all chronic myelogenous leukemia
phosphorylation role in cellular signaling
- Phosphorylation involves the addition of a phosphate group to a protein molecule, by enzymes called kinases—this helps regulate function and activity of the cell
- Phosphorylation serves as a molecular switch, turning proteins “on” or “off” in response to specific cues
*phosphatase reverse phosphorylation (releasing inorganic phosphate)
**Phosphorylation is a cell’s way of fine tuning on and off signals
depending on what other signals it receives and its environment
what are the ways cell signaling can be regulated
-phosphorylation
-upregulation
-direct binding to change conformation
A acivates B, B inhibits C, C inhibits E.
If you have more A, what happens to E?
If you have more A, which activates B, it would likely lead to an increase in B activity. Since B inhibits C, this increased B activity would result in decreased C activity. As C inhibits E, a decrease in C activity would mean less inhibition of E, possibly resulting in increased E activity. So, in summary, having more A could lead to an increase in E activity
A acivates B, B inhibits C, C activates D.
If you have more A, what happens to D?
If C is being inhibited due to increased B activity, then there would indeed be less activation of D, resulting in decreased D activity. So, with more A leading to increased inhibition of C, the likely outcome would be a decrease in the activity of D.
A acivates B, B inhibits C, C inhibits E, and E inhibits A.
If you have more A, what happens to A over time?
With more inhibition of C, there’s more E being produced. And with more E being produced, more E inhibits A, leading to less A over time
Proto-oncogenic kinases examples
***Raf
*MEK
*ERK
*mTOR
*AKT
PDK1
**P13K
types of proto-oncogene examples:
*Rheb
Raptor
**Ras
tumor suppressors examples:
***PTEN
*TSC1 and TSC2
Ras P13K signaling
Ras signaling:
- Ligand binds to RTK.
- Signaling is initiated then by IRS
- IRS activates Ras
- Ras activates Raf
- Raf activates MEK
- MEK activates ERK
Result: cell cycle progression and proliferation
