Lecture 15

Question 1

Characteristics of cancer cells

Answer 1

• divide continually and quicker than normal cells
• contain heritable mutations
• transplantable
• dedifferentiated
• have a different appearance
• cell surface has different types and/or number of antigen
• lack contact inhibition
• induce angiogenesis
• invasive
• metastasize

Question 2

dedifferentiated (characteristic of cancer cell)

Answer 2

lose their specialized identity

Question 3

angiogenesis

Answer 3

formation of local blood vessels

Question 4

invasive (characteristic of cancer cell)

Answer 4

squeeze into any space available

Question 5

metastasize (characteristic of cancer cell)

Answer 5

move to new location in body

Question 6

origins of cancer cell (4)

Answer 6

• activation of stem cells that produce cancer cells
• dedifferentiation - lose their specialized identity
• increase in proportion of a tissue that consists of stem cells or progenitor cells
• faulty tissue repair

Question 7

cancer by loss of specialization

Answer 7

specialized cells lose some of their distinguishing features as mutations occur when they divide
-result: dedifferentiation

Question 8

what can cause cancer?

Answer 8

• loss of specialization
• shifting balance of cell types in a tissue
• uncontrolled tissue repair

Question 9

acute vs chronic injury

Answer 9

acute: resting epithelium –> injury and activation of tissue –> repair (–> injury and activation of tissue)
chronic: persistent activation of stem cells –> cancer

Question 10

proto-oncogenes

Answer 10

normal versions of genes that promote cell division

Question 11

What happens when expression is at the wrong time or in the wrong cell type?

Answer 11

it leads to cell division and cancer

Question 12

oncogenes

Answer 12

proto-oncogenes in their mutated form

Question 13

how many copies of an oncogenic mutation is sufficient to promote cell division?

Answer 13

one copy

Question 14

oncogenes: overexpression of a normal function

Answer 14

overexpression of the proto-oncogene is caused by moving a proto-oncogene next to a highly transcribed gene

Question 15

when is an oncogene activated?

Answer 15

when a proto-oncogene moves next to another gene. the gene pair is transcribed together

Question 16

fusion protein

Answer 16

the double gene product

-it activates or lifts control of cell division

Question 17

Chronic Myelogenous Leukemia (CML)

Answer 17

-Most patients have a translocated Philadelphia chromosome (tip of 9 on 22)
-Abl (chromosome 9) and bcr (chromosome 22) genes produce a fusion protein
-BCR-ABL oncoprotein is a tyrosine kinase that excessively stimulates cell division
-Understanding cellular changes allowed development of new drug, Gleevec, for
treatment

Question 18

Her-2/neu

Answer 18

-Product of an oncogene
Excessive levels in approximately 25% of breast cancer patients
-Too many receptors
-Too many signals to divide
-Monoclonal antibody drug, Herceptin, binds to receptors, blocking signal to divide

Question 19

tumor suppressor genes

Answer 19

• Cancer can be caused by loss of genes that inhibit cell division
• Tumor suppressor genes normally stop a cell from dividing
• Mutations of both copies of a tumor suppressor gene is usually required to allow cell division
• Genes can also be lost by deletion or silenced by promoter hypermethylation

Question 20

Retinoblastoma (RB)

Answer 20

-The RB gene is on chromosome 13
-The RB protein binds transcription factors so that they cannot activate genes that carry
out mitosis. Normally halts the cell cycle at G1
-Study of RB was the origin of the “two-hit” hypothesis of cancer causation

Question 21

two-hit hypothesis

Answer 21

-Two mutations or deletions are required. One in each copy of the RB gene
-For sporadic cases (non-inherited). Retinoblastoma is a result of two somatic
mutations
-For familial cases (inherited), individuals harbor one germline mutant allele for the RB gene in each of their cells. This is followed by a somatic mutation in the normal allele

Question 22

p53

Answer 22

-The p53 gene is the “guardian of the genome”
-Determines if a cell has repaired DNA damage
-If damage cannot be repaired, p53 can induce apoptosis
-More than 50% of human cancers involve an abnormal p53 gene
-Rare inherited mutations in the p53 gene cause a disease called Li-Fraumeni syndrome
- Family members have many different types of
cancer at early ages

Question 23

What are the two main forms of breast cancer?

Answer 23

1. Familial form: A germline mutation is inherited and then a somatic mutation occurs in a breast cell
2. Sporadic form: Two somatic mutations affect the same cell

Mutations in many genes can cause cancer

Question 24

BRCA

Answer 24

-The two major breast-cancer susceptibility genes are BRCA1 and BRCA2
- Encode proteins that join two others to form a complex that allows repair of double-stranded DNA breaks
-Mutations in these genes have different incidences in different populations
-Inheriting BRCA mutations increases the risk
of other types of cancer

Question 25

Other genes

Answer 25

genes whos protein products affect those of BRCA1, BRCA2, and p53 can cause breast cancer

Question 26

gatekeeper genes

Answer 26

directly control mitosis and apoptosis

Question 27

caretaker genes

Answer 27

control mutation rates and may have an overall effect, when mutant, in destabilizing the genome

Question 28

How can people lower the chance of developing cancer?

Answer 28

- avoiding high-risk environmental factors, such as smoking and excess sun exposure - taking "chemopreventative" nutrients such as folic acid and vitamin D - cruciferous vegetables

Question 29

method to study cancer - population study

Answer 29

compares incidence of a type of cancer among different groups of people

Question 30

method to study cancer - case control

Answer 30

identify differences between patients with a type of cancer and healthy individuals matched for mutiple characteristics

Question 31

method to study cancer - prospective studies

Answer 31

two or more groups of individuals follow a specific regimen (e.g. , det or activity plan) and are checked regularly for cancer

Question 32

Cancer treatment

Answer 32

``` New types of cancer drugs: - Stimulate cells to regain specialized characteristics - Inhibit telomerase - Induce apoptosis - Inhibit angiogenesis Genomics information is increasingly used - Enables physicians to better matchpatient to treatment ```

Question 33

cytogenetics

Answer 33

a subdisipline within genetics. deals with chromosome variations. - excess genetic material has a milder effects on health than a deficit - still, most large-scale chromosomal abnormalities present in all cells disrupt or halt prenatal development

Question 34

what are the essential parts of a chromosome?

Answer 34

telomeres origins of replication sites centromere

Question 35

portrait of a chromosome - heterochromatin

Answer 35

darkly staining | -consists mostly of repetitive DNA

Question 36

portrait of a chromosome - euchromatin

Answer 36

lighter straining | -contains most protein-encoding genes

Question 37

portrait of a chromosome - telomeres

Answer 37

chromosome tips composed of many repeats of TTAGGG | -shorten with each cell division

Question 38

centromeres

Answer 38

the largest constriction of the chromosome and where spindle fibers attach - the bases that form the centromere are repeats of a 171-base DNA sequence - replicated at the end of S-phase; facilitated by centromere protein - CENP-A is passed to next generation - an example of an epigenetic change

Question 39

subletelomeres

Answer 39

the chromosome region between the centromere and telomeres - consists of 8,000 to 300,000 bases - near the telomere, the repeats are similar to the telomere sequence - contains at least 500 protein-encoding genes - about 50% are multigene families that include pseudogenes

Question 40

how many chromosome types do humans have?

Answer 40

- autosomes are numbed 1-22 by size - sex chromosomes are X and Y karyotype - a chromosome chart

Question 41

centromere positions

Answer 41

At tip – Telocentric Close to end – Acrocentric Off-center – Submetacentric At midpoint – Metacentric

Question 42

how are karyotypes useful

Answer 42

1) can confirm a clinical diagnosis 2) can reveal effects of environmental toxins 3) can clarify evolutionary relationships

Question 43

how to visualize chromosomes

Answer 43

chromosomes are extracted then stained with a combination of dyes and DNA probes

Question 44

how is tissue obtained from a person?

Answer 44

``` Tissue is obtained from person - Fetal tissue: Amniocentesis Chorionic villi sampling Fetal cell sorting Chromosome microarray analysis - Adult tissue: White blood cells Skinlike cells from cheek swab ```

Question 45

Amniocentesis

Answer 45

how fetal (15-16 months) tissue is obtained - detects about 1,000 of the more than 5,000 known chromosomal and biochemical problems - fetal cells suspended in the fluid around the fetus are sampled - ultrasound is used to follow needle's movement

Question 46

chrionic villi sampling

Answer 46

-Performed during 10-12th week of pregnancy - cels of the chorion are sampled -Provides earlier results than amniocentesis -However, it does not detect metabolic problems - And has greater risk of spontaneous abortion

Question 47

fetal cell sorting

Answer 47

-Fetal cells are distinguished from maternal cells by a fluorescence-activated cell sorter - Identifies cell-surface markers -A new technique detects fetal mRNA and DNA in the bloodstream of the mother

Question 48

FISH (fluorescene in situ hybridization)

Answer 48

DNA probes labed with fluorescing bind complementary DNA | -fluorescent dots correspond to copies of chromosome 21