Molecular Carcinogenesis

Front 1

How many mutations are typically needed to create a cancer cell?

Back 1

6-10

Front 2

Name the 6 hallmarks of cancer

Back 2

Evading apoptosis
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion & metastasis
Limitless replicative potential (becoming immortal)
Sustained Angiogenesis
(maybe a 7th = Ability to avoid the immune system)

Front 3

True or False

A cancer is made up of one type of mutated cells

Back 3

False:
A tumor is like an organ, it is self sufficient and can recruit all kinds of tissues.

Front 4

What are the three factors to consider in solid tumor staging?

Back 4

T = Tumor Size
N = Node Status
M = Distant Metastasis (not to local nodes)

Front 5

Is tumor grade a subjective or an objective evaluation?

Back 5

Subjective

Front 6

Is tumor stage a subjective or an objective evaluation?

Back 6

Objective

Front 7

What are three subjective factors that make up grade in breast cancer?

Back 7

Nuclear Pleomorphism
Mitotic Figures
Tubule Formation

Front 8

What is pleomorphism in relation to the nuclei of cancer cells?

Back 8

odd shaped nuclei

Front 9

In looking at the grade of a cancer the pathologist looks for mitotic figures. What is this and what kind of finding would suggest a higher grade?

Back 9

Mitotic figures are the number of cells in mitosis in the field of a microscope.
A higher number indicates a higher grade.

Front 10

S-phase fraction is an objective factor considered in staging cancer. How do you define it, and what would indicate a higher stage?

Back 10

The number of cells in the DNA replication phase (S-phase).
Usually we don't have a lot of cells in division.
More cell division = higher stage.

Front 11

Aneuploidy is another objective factor evaluated when staging a tumor.
What is aneuploidy?

Back 11

An abnormal number of chromosomes.

Front 12

What kind of tubule formation would you see in normal breast tissue as opposed to cancer of the breast.

Back 12

Normal tissue has tubules that stain as dark blue circles. In cancer the tubules are not distinct structures. In cancer you don't see normal tubule formation.

Front 13

What kind of information can you get from looking at the molecular status of a tumor?

Back 13

Prognostic, Predictive, and Therapeutic information. By knowing what kinds of molecular features a tumor has you can assess the likelihood that a patient will respond to a certain treatment.

Front 14

What does prognostic information tell you?

Back 14

Overall Survival = how long a patient might live
Disease Free Survival = how long a patient might live without a cancer coming back?

Front 15

If the provider says the prognosis is about 4 months, does that mean the patient will live about 4 months and then die?)

Back 15

No, a prognosis of 4 months means that by 4 months half of people in a similar situation will have died and half will be alive.

Front 16

Which breast cancers respond to the drug Herceptin

Back 16

Those with Her2Nu Receptors

Front 17

The philadelphia chromosome (abnormally short 22) causes CML:
(Chronic Myeloid Anemia).

We see a translocation and resulting fusion of from chromosome 9 and 22.

What is the name of the abnormal fusion gene?

Back 17

BCR-ABL (translocation between "B Cell Receptor and ABL kinase"

the ABL gene is normally on 9 and encodes a tyrosine kinse enzyme, in the ABL-BCR gene a large portion of the proto-oncogene called ABL is translocated to the BCR gene on 22 - the result is uncontrolled tyrosine kinase activity.

The drug Imatinib Mesylate (Gleevec) is used as targeted therapy - it inhibits tyrosine kinase

Front 18

What molecular marker do we look for in in evaluating colon cancer?

Back 18

EGFR = Epidermal Growth Factor Receptor

Colon cancers with this receptor are responsive to EGFR inhibitors

Front 19

Which breast cancers respond to Tamoxifen?

Back 19

ER (estrogen receptor) positive tumors.

Tamoxifen binds the estrogen receptors so that estrogen can't stimulate growth in the tumors.

Front 20

What receptors are breast cancers evaluated for?

Back 20

ER = estrogen receptors
PgR or PR = Progesterone receptors
Her2Nu = Human Epidermal Growth Factor Receptor 2

Front 21

There are two approaches molecular biologists take to try to identify markers that have prognostic and/or predictive benefit. Name these two approaches

Back 21

Candidate gene approach

Genomics/ gene expression profiling

Front 22

What is the term that relates to post-transational modifications? (i.e. these are alterations in DNA that don't result in mutation, there is no change in sequence, but they alter the expression of genes. For example, how tightly they are wound through methylation acetylation, farnesylation , phosphorylation.

Back 22

Epi-Genetic

Front 23

True of False:

Chemotherapy is a targeted gene approach to treating cancers.

Back 23

False - chemotherapy is like a sledgehammer. It blocks anything that is dividing. It is the main standard of care for all cancers.

Front 24

True or False:

Most breast cancers are ER positive

Back 24

True:

about 70% are ER positive. However about 30% of these will fail hormone therapy because they develop a hormone independent way to survive.

Front 25

What is the 10 year survival rate in women under 50 years of age treated with chemotherapy?
(give rates for both node negative and node positive)

Back 25

71-78% for node negative patients 42-53% for node positive patients

Front 26

True or False:

Most breast cancer patients don't benefit from chemotherapy.

Back 26

True:

Most patients would not have a cancer that would have ever spread, so they didn't need the chemotherapy.

This is why we say that breast cancer is grossly overtreated. However, if the cancer does progress and spread, then there is nothing that can be done to save the patient.

Front 27

Which breast cancer patients are more likely to need chemotherapy?
ER negative or ER positive?

Back 27

ER negative patients will ALWAYS be given chemo.

Most ER positive patients probably don't need chemo.

Front 28

How is microarray technology for gene-expression profiling different from candidate gene approach in terms of trying to find markers with prognostic and predictive value?

Back 28

With microarray technology we are looking at every gene in the whole genome rather than just looking "under the lamp" or in other words we are not limited by our current understanding of the cancer, the genes, and their functions.

Front 29

What do the little red and green dots mean on the microarray read outs?

Back 29

Green = genes expressed only in normal tissue.

Red = genes expressed only in the tumor tissue.

Front 30

What kinds of things can impact the expression of a gene in a tumor besides a predisposition or cause of cancer?

Back 30

Many things, from the person's genetic background, to what they ate that morning.

Front 31

When we analyze microarray data we take many different individuals and look at the expression of genes in their genome and in their tumor.
In using computerized analysis to classify cancer what are the three general strategies used to classify cancer?

Back 31

Unsupervised Analysis and Classification:

Supervised Analysis: select genes that seem to associate with a particular clinical phenotype (e.g. relapse, node status etc)

Hypothesis: select genes based on physiology and functional mechanism shown in a model system.