Malignancies Flashcards by Stacey Hansen

RAS activates this pathway

PI3K pathway

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This pathway leads to progrowth metabolism (Warburg)

PI3K pathway
Activated by Ras

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RAS activates this transcription factor which stimulates production of MYC and cyclins

BRAF

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BRAF is activated by RAS and induces production of these 2

MYC and cyclins

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BRAF is activated by Ras and induces production of this, which leads to pro-growth pathways

MYC

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This is dysregulated in neuroblastoma

MYC

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Proteins that cause progression through the cell cycle

Cyclins

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Cyclins attach to and activate these

Cyclin dependent kinases (CDKs)

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These attach to and activate cyclin dependent kinases (CDKs)

cyclins

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These phosphorylate various proteins to produce growth, division, metabolic effects
Lose activity when the attached cyclin degrades

Cyclin dependent kinases (CDKs)

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Two checkpoints in the cell cycle

Between G1-S progression and G2-M progression

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This cyclin binds CDK4

Cyclin D

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Cyclin D binds this CDK

CDK4

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MYC stimulates this cyclin pathway

Cyclin D

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This stimulates the cyclin D pathway

MYC

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This is inactivated and allows S phase entry

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Tumor suppressor gene that is lost in Familial Retinoblastoma

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Translocation in mantle cell lymphoma

t(11:14) of cyclin D

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Ras may be dysregulated by this type of mutation

Gain of function

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This inhibits many proto-oncogenes

p53

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Tumor suppressor gene that inhibits cyclin dependent kinase (CDK4-Cyclin D complex)
Often lost in melanoma

p16

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p16 inhibits this

Cyclin dependent kinase (CDK4-cyclin D complex)

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Tumor suppressor gene that is often lost in melanoma

p16

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PTEN inhibits this

PI3K

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This inhibits PI3K

PTEN

This inhibits E2F transcription factor

Rb inhibits this transcription factor

E2F

Is RAS active or inactive when phosphorylated?

Active

To prevent inappropriate growth, these immediately dephosphorylate the RAS-GTP to its inactive form

GAP proteins Are tumor suppressor proteins

GTPase activating protein (tumor suppressor gene) that normally inactivates RAS:GTP --> GDP, and when lost causes neurofibromatosis 1

NF1

Tumor suppressor gene that inhibits PI3K/AKt signaling

PTEN (phosphatase and tensin homologue)

Autosomal dominant disorder involving loss of function mutation of NF1 (GAP)

Neurofibromatosis 1

Neurofibromatosis 1 is caused by this

Loss of function mutation of NF1 gene

Autosomal dominant disorder caused by a loss of function mutation in PTEN gene

Cowden syndrome

Cowden syndrome is caused by this

Loss of function mutation of PTEN gene

Endometrial carcinoma, breast carcinoma, thyroid cancer, hamartomatous intestinal polyps and hamartomatous skin lesions are features of this condition

Cowden syndrome

Active form of Rb tumor suppressor gene is this

Hypophosphorylated

This binds and inactivates E2F, a pro-growth transcription factor

Rb binds and inactivates this

E2F, a pro-growth transcription factor

E2F is this

Pro-growth transcription factor

Autosomal dominant condition involving the inheritance of one allele, so only one more cell needs a mutation to produce a tumor

Familial Retinoblastoma

Inherited loss of a p53 copy (one hit) 25x risk of malignancy by age 50 Sarcomas, adrenal carcinoma, breast cancer, leukemia

Li-Fraumeni Syndrome

Li-Fraumeni Syndrome is an inherited loss of this

A p53 copy

Sarcomas and adrenal carcinoma are characteristic of this condition caused by loss of p53 copy

Li-Fraumeni Syndrome

Tumor suppressor gene lost in colon cancer

APC Part of WNT signaling pathway to stabilize beta-catenin, a co-transcription factor

Part of WNT signaling pathway to stabilize beta-catenin, a co-transcription factor Lost in colon cancer

APC

APC is a tumor suppressor gene lost in this

Colon cancer

Tumor suppressor gene lost in signet ring cancer of breast and stomach

CDH1

Tumor suppressor gene that encodes E-cadherin adhesion molecule

CDH1

Tumor suppressor gene lost in renal cell carcinomas

VHL

Gain of function of these lead to neoplasia

Oncogenes

Loss of function mutations of these lead to neoplasia

Tumor suppressor genes

Often a single mutation of these is needed for neoplasia (dominant pattern of inheritance)

Oncogenes

Usually need loss of both genes of these for neoplasia (recessive pattern of inheritance)

Tumor suppressor genes

Growth promoting metabolic alterations Cells enter preferential fermentative metabolism Provides excess carbon macromolecules at expense of energy

Warburg effect

p53 is this type of apoptotic force

Pro-apoptotic

bcl-2 is this type of apoptotic force

Anti-apoptotic

This is over-expressed in follicular lymphoma t(14;18)

bcl-2

Over-expression of this results in slow-growing, indolent tumors Incurable because low proliferation

bcl-2

Proteins that form channels in mitochondrial membrane

Bax/Bak

Protein that binds bax/bak and prevents its dimerization Results in no mitochondrial permeability

Bcl-2

This protein activates bax/bak and relocates to mitochondrion Results in increased mitochondrial permeability and caspase activation

p53

Cellular immortality most often involves this mechanism

Telomere

Some cancers reactivate telomerase function, and this is one mechanism

loss of p53

Some cancers have intrinsic telomerase activity by this method

Retain stem cell population

New vascular supply is needed for tumors to grow beyond this

1-2 mm

This type of tumor environment promotes HIF-enabled transcription

Ischemic

This inhibits VEGF Loss allows VEGF to promote vessel growth (tumor angiogenesis)

p53

Monoclonal antibody that inhibits VEGF

Bevacizumab

Bevacizumab inhibits this

VEGF Prevents angiogenesis

Transcription factor activated in ischemic tumor environment that promotes transcription of VEGF

Hypoxia inducible factor (HIF)

Cell adhesion molecule that is often lost or suppressed to allow metastatic epithelial cells to detach from each other

E-cadherin

In normal cells, epithelial integrins bind this on the matrix

Laminin

In normal cells, these bind matrix laminin

Epithelial integrins

In cancer, this is lost, which usually binds matrix laminin Allows cells to attach to remodeled matrix

Integrin

In cancer, matrix is induced to produce this Allows cells to attach to remodeled matrix

Fibronectin

Morphological stromal reaction to invasion

Desmoplasia

In order to survive intravascular travel, metastatic cells use this coating for stability and evasion of surveillance

Platelet

2 complementary adhesion molecules that allow metastatic cancer cell implantation in bone

E-cadherin and osteoblast N-cadherin

Antigens on tumor cells which are not recognized as self-antigens

Neoantigens

Tumor cells upregulate this which inhibits APCs

CTLA-4

Tumor cells upregulate CTLA-4, which inhibits this

APCs

2 proteins that tumor cells upregulate in order to inhibit/avoid T cell killing

CTLA-4 (inhibits APCs) PD-L1 and PD-L2

Anti-CTLA-4 antibody

Ipilimumab

Ipilimumab is a monoclonal antibody against this

CTLA-4

Pembrolizumab and Nivolumab are antibodies against this

PD-1

Atezolizumab, Avelumab and Durvalumab are antibodies against this

PD-L1

Most frequently mutated gene in human cancer

p53

Normally p53 is inactivated by this

MDM2 ubiquitination

Protein that is normally inactivated by MDM2 ubiquitination

p53

Stressed cells have decrease MDM2 binding, which increases activity of this

p53

Stressed cells have decreased binding of this, which results in increased p53 activity

MDM2

This maintains Rb in active hypophosphorylated form

p21

p21 maintains this in active hypophosphorylated form

p53 increases activity of this CDK-inhibitor which maintains Rb in active hypophosphorylated form

p21

p53 can increase transcription of this to increase mitochondrial permeability and induce apoptosis

BAX

Tandem nucleotide repeats, normally of uniform constant length Hallmark of loss of mismatch repair enzymes

Microsatellite instability (MSI)

Microsatellite instability (MSI) is hallmark of this

Loss of mismatch repair enzymes

Syndrome of defective MMR enzymes

Lynch syndrome

System to excise and correct pyrimidine residues cross-linked by UV radiation

Nucleotide excision repair

Disorder of NER enzyme loss of function (defect in components of excision repair) HIGH rates of UV induced skin cancers (Squamous cell and Basal cell)

Xeroderma Pigmentosa

Repair of double stranded DNA breaks and DNA cross-links

Homologous recombination

Condition caused by Mutations/defects in Homologous recombination factors Aplastic anemia, leukemia

Fanconi anemia

Cells that normally break and rejoin DNA, and errors in this produce frequent translocations

Lymphoid cells

Translocation in Burkitt Lymphoma

t(8:14)

Translocation of t(8:14) is characteristic of this

Burkitt Lymphoma

Translocation of t(14:18) is characteristic of this

Follicular lymphoma

Translocation of t(11:14) is characteristic of this

Mantle cell lymphoma

Translocation in Follicular Lymphoma

t(14:18)

Translocation in Mantle Cell Lymphoma

t(11:14)

Chemical carcinogen that preferentially causes specific mutation in TP53 codon 249

Aspergillus aflatoxin

Aspergillus aflatoxin results in this condition

Hepatocellular carcinoma

Hepatocellular Carcinoma can be caused by this chemical carcinogen

Aspergillus Aflatoxin

Aflatoxin preferentially causes this specific mutation

TP53 codon 249 (G:C --> T:A)

Type of specific UV radiation that produces pyrimidine dimers, especially T-T pairing

UV-B (280-320 nm)

Acute myeloid leukemia and Thyroid malignancies can be produced from this

Ionizing radiation

Infection that infects B cells via CD21 (complement receptor)

EBV

EBV infects these cells

B cells

EBV infects B cells via this

CD21, complement receptor

Infection that binding produces viral encoded proteins, LMP-1 and EBNA-2

EBV

Viral encoded proteins produced from EBV infecting B cells via CD21

LMP-1 and EBNA-2

Viral encoded protein with stimulated CD40 activated form that mimics helper T cell signaling, leading to B cell proliferation; also activates bcl2 and prevents apoptosis

LMP-1

The viral encoded protein LMP-1 results in these 2 main actions

B cell proliferation Prevents apoptosis

Viral encoded protein EBNA2 activates this

Cyclin D1 (leads to proliferation)

Viral encoded protein that activates Cyclin D1, leads to proliferation

EBNA2

EBV results in polyclonal B cell proliferation, and this condition

Infectious Mononucleosis

What most commonly causes infectious mononucleosis?

EBV infection

Infectious mononucleosis involves proliferation of these cells as a result of EBV infection

Polyclonal B cell proliferation

EBV infection in patient with deficient immune system increases likelihood of this

t(8:14) = Burkitt lymphoma

This type of infection in patient with deficient immune system increases likelihood of t(8:14), leading to Burkitt Lymphoma

EBV

Microbial infection that can cause adult T cell leukemia/lymphoma

HTLV1

Microbial infection that can cause mucosal squamous cell carcinomas

HPV 16/18

Microbial infection that can cause gastric carcinoma and gastric MALT lymphoma

H. pylori

Microbial infection that can cause hepatocellular carcinoma

Hep C and B

Microbial infection that can cause nasopharyngeal carcinoma

EBV

Microbial infection that can cause B cell lymphomas in immune suppressed patients

EBV

These tumors often are functional

Endocrine

Parathyroid adenoma secretes these hormones

Prolactin, ACTH

Adrenal tumor secretes these hormones

Catecholamines (epinephrine)

Pancreatic tumor secretes this

Insulin

Signs and symptoms due to tumor but not explained by mass or function of tissue of origin

Paraneoplastic syndromes

Hypercatabolic state not explain by low caloric intake Fat and muscle loss Most often with advanced cancers Thought to be due to TNF; other inflammatory mediators

Cancer Cachexia

A category used to predict behavior based on the tumor morphology Sometimes uses Degree of Differentiation

Tumor grade

An assessment of the extent of tumor spread

Tumor stage

What is tumor grade?

Category used to predict behavior based on the tumor morphology

What is tumor stage?

Assessment of the extent of tumor spread (describes what the tumor has already done)

3 components of tumor stage

T = primary tumor spread (tumor size, invasion of specific structures, vascular invasion) N = are lymph nodes involved M = metastases beyond lymph nodes

Malignancies Flashcards

(147 cards)