Unit 3 - Formative 7 D2

Front 1

Tumor Heterogeneity

Back 1

A tumor is a mix of benign and malignant cells; this can effect the therapy administered

Mutations later down the line (4th or later in the slides) become malignant

Front 2

Proto-oncogenes

Back 2

Stimulate normal cell proliferation

Front 3

Tumor suppresor genes

Back 3

Normally inhibit cell proliferation

Front 4

Regulators of apoptosis

Back 4

Pro and anti cell deathDNA

Front 5

DNA Repair Genes

Back 5

Maintain genomic stability, indirectly regulate cell proliferation;

Front 6

Philadelphia Chromosome

Back 6

bcr-abl hybrid (chimeric gene) resulting in chronic myeloid leukemia (CML)

"Philadelphia CreaML cheese"

Front 7

How would a mutation in DNA repair genes cause?

Back 7

Increases genomic instability and mutation in proto-oncogenes and tumor suppressors

Front 8

Frequency of sporadic vs inherited forms of cancer?

Back 8

Sporadic (90%)
Inherited (5-10%); mutation in germline so ALL the cells carry the mutation instead of just one as in a sporadic mutation

Front 9

c-myc

Back 9

Oncogene; Burkitt's lymphoma

Front 10

ras

Back 10

Oncogene; Colon carcinoma

Front 11

Rb

Back 11

Tumor suppressor gene; retinoblastoma

Front 12

p53

Back 12

Most human cancers

Front 13

What type of receptor do growth factors bind to?

Back 13

Receptor Tyrosine Kinases

Front 14

These proto-oncogenes are the most commonly mutated

Back 14

Ras

Front 15

Which pathway does Ras use for signaling?

Back 15

MAPK, which is critical for proper cell cycle regulation

Front 16

Gene amplification of N-Myc is linked to what tumor?

Back 16

Neuroblastoma

Front 17

What is the principle role of Myc related to the cell cycle?

Back 17

Increase the transcription of the G1 cyclins (also called the D cyclins)

Front 18

Which two cyclin-Cdk pair is required to pass the restriction point in the cell cycle?

Back 18

Cdk-4 and cyclin D

Front 19

What two things are required to active Cdks?

Back 19

1. binding of their appropriate cyclin
2. phosphorylation by an upstream kinase called a Cdk-activating kinase (CAK)

Front 20

How are Rb and E2F protein related?

Back 20

E2F -> dna synthesis
E2F + Rb -> inactivated

Front 21

Activation of p53 induces what

Back 21

Cell cycle arrest and apoptosis

Front 22

Apoptosis vs Necrosis

Back 22

Apoptosis: Cell destruction w/o inflammatory response
Necrosis: Cell destruction w/ inflammatory response

Front 23

Caspases

Back 23

cysteine-aspartic-proteases; play essential roles in apoptosis

Front 24

Extrinsic Apoptotic Pathway

Back 24

Fas death receptor binds Fas ligand; recruit of FADD adaptor protein which recruits procaspase 8 or 10 -> apoptosis

Front 25

Intrinsic Apoptotic Pathway

Back 25

Cytochrome c + procaspase 9 -> adaptor protein (apoptosome) -> executioner caspases activated -> apoptosis

Front 26

Bcl2

Back 26

Inhibits BH123 (Bax or Bak) channel from releasing cytochrome c

Bcl2 is an oncogene associated with B-cell lymp

Front 27

What apoptotic stiulus protein inactivates anti-apoptotic Bcl2 protein?

Back 27

BH-3 only proteins (Bad and Bid)

Front 28

Loss of heterozygosity

Back 28

1. inactivating mutation in one allele of a tumor suppressor gene occurs in germline cell
2. LOH occurs when remaining functional allele becomes inactivated by mutation

Front 30

How can loss of APC function lead to deregulated cell proliferation?

Back 30

PREDISPOSITION for developing cancer is inherited (100% penetrance); los of heterozygosity required for colon cancer development

Front 31

Hereditary Nonpolyposis Colorectal Cancer

Back 31

Inherited defects in DNA repair mechanisms = genetic instability (compared to FAP which only predisposes to cancer)

Front 32

Describe how an accumulation of mutations in a single somatic cell lineage gives rise to cancer

Back 32

1. One mutant APC gene
2. LOH at another APC gene
3. K-RAS mut
4. p53 LOH

Front 33

Increased transcription of B-catenin/Tcf increases what cyclin protein

Back 33

cyclin D

Front 34

Function of cyclin D

Back 34

G1 -> S in cell cycle

Front 35

Adenoma

Back 35

Benign tumor of glandular origin

Hyperplastic growth; no disruption of the basement membrane

Front 36

Invasive Carcinoma

Back 36

Invasive malignant tumor consisting of transformed epithelial cells
Penetration through the basement membrane; infiltration into submucosa and beyond

Front 37

What is the ratio of cancer stem cells to transit amplifying cells in a tumor mass?

Back 37

Cancer stem cells are the minority; transit amplifying cells are the majority

Front 38

Despite the tremendous genetic and phenotypic heterogeneity, why are tumors considered to be monoclonal?

Back 38

Because tumorigenesis still ocurs at the level of a single cell

Front 39

Describe the concept of darwinian evolution and clonal succession o ftumor cells

Back 39

One cell amid a large population acquires a mutation that confers a proliferative advantage over its siblings