Neoplasia II

Question 1

Metastasis definition

Answer 1

Development of secondary deposits of a tumor in a distant site
Considered the hallmark of malignancy (but not always seen)

Question 2

T/F - All cancers have the same rate of metastasis

Answer 2

False - some types of cancer metastasize

Question 3

How often do tumors metastasize?

Answer 3

30% of newly diagnosed patients with solid tumors will already have obvious metastases
Another 20% will have occult metastases

Question 4

What kinds of tumors are more likely to metastases

Answer 4

In general, the larger and more anaplastic (less differentiated) a tumor is, the more likely it is to metastasize

Question 5

What are the ways Metastasis spread?

Answer 5

Seeding within body cavities
Lymphatic spread
Hematogenous spread

Question 6

Lymphatic spread of metastasis

Answer 6

Usually seen with carcinomas

Lymph nodes are involved - leads to lymph node metastases

Question 7

Hematogenous spread

Answer 7

Usually seen with sarcomas

Liver and lungs are most often affected

Question 8

Cancer Epidemeology

Answer 8

Often provides clues as to the etiology (cause) of or contributing factors to cancer development

Question 9

Geography and Environment effect on cancer

Answer 9

Sometimes clues as to cancer etiology can be obtained by looking at the cancer incidence of specific countries, populations, or geographic regions and identifying particular habits, dietary features, etc that might contribute to an increased incidence of a particular type of cancer

Question 10

How does age effect cancer rate

Answer 10

Cancer frequency often increases with age
Most cancer mortality occurs between 55-75 years of age
Yet, 10% of deaths among children

Question 11

Heredity of Cancer

Answer 11

Cancer occurs in 1 of 5 people

There are predisposing factors for some cancers, but well-defined genetic influences are only identified in a few

Question 12

What are the 3 broad categories of genetic predisposition to cancer

Answer 12

1) Inherited cancer syndromes
2) Familial cancers
3) Defective DNA repair

Question 13

Inherited Cancer

Answer 13

Usually due to a single gene mutation and generally show autosomal dominant transmission
examples:
-Retinoblastoma
-Familial adematous polyposis
-Multiple endocrine neoplasia

Question 14

Familial Cancers

Answer 14

Early age at onset
Tumors arising in two or more close relatives of the index case
Colon, breast, ovary and brain malignancies have been reported to occur in familial patterns

Question 15

What are some Acquired Preneoplastic Disorders?

Answer 15

Increased liklihood of cancer in:

• persistent regenerative cell replication
• villous adenomas of the colon
• leukoplakia of oral or genital mucosa

Question 16

What lies at the heart of carcinogenesis?

Answer 16

Nonlethal genetic damage

Question 17

The fact that most cancers are clonal proliferations suggests what?

Answer 17

That tumors arise from one genetically altered cell

Question 18

What are the 3 classes of normal regulatory genes that are often effected in carcinogenesis?

Answer 18

Protooncogenes - growth promoting
Cancer suppressor genes - growth inhibiting
Apoptosis genes

Question 19

DNA repair genes

Answer 19

Indirectly contribute to cancer development since acquire mutations can’t be repaired
-if these genes are disabled, the frequency of mutations increases, and the rate of neoplastic transformation increases

Question 20

T/F - Carcinogenesis is a multi-step process

Answer 20

True - at both the phenotypic and genetic levels

Question 21

What are the products of oncogenes?

Answer 21

Oncoproteins

Question 22

How are protooncogenes transformed to oncogenes?

Answer 22

1) Structural mutation of the gene, resulting in an abnormal product
2) Altered regulation of gene expression, resulting in increased production of a normal growth-promoting pattern

Question 23

What are some examples of proteins that when are effected can lead to uncontrolled promotion of cell growth?

Answer 23

Growth Factor
Growth Factor receptors
Signal-transducing proteins
Nuclear transcription
Cyclins and cyclin-dependent kinases

Question 24

Growth Factors oncoproteins

Answer 24

All normal cells require growth factor stimulation to undergo proliferation
examples:
-platelet derived growth factor (PDGF)
-TGFa

Question 25

Growth Factor Receptor oncoproteins

Answer 25

Mutations and over expression of growth factor receptors have been documented
Mutant receptor proteins deliver continuous mitogenic signals
Overexpression makes cancer cells hyperresponsive to even normal GF levels

Question 26

Signal-Transducing oncoProteins

Answer 26

RAS - approximately 20% of all human tumors contain mutated RAS oncogene
Normally inactivated quickly, mutant RAS remains in its active form, stimulating constant cell proliferation

Question 27

Nuclear Transcription Factor oncoproteins

Answer 27

MYC gene is most commonly effected
MYC gene dysregulation leads to overexpression, leading in continuous activation of cyclin-dependent kinases (CDKs) driving the cell to divide
MYC also represses CDK inhibitors

Question 28

Cyclins and Cyclin-dependent Kinase oncoproteins

Answer 28

Orderly progression of cell cycle is orchestrated by CDKs following activation by binding to cyclins
Activity of CDKs is regulated by two families of CDK inhibitors (CDKIs)
Dysregulation favors cell proliferation

Question 29

Tumor Supression Genes

Answer 29

Products inhibit cell proliferation
RB (retinoblastoma) gene was first to be discovered - products regulates transcription
Products are generally less understood than those of oncogenes
Regulate cell cycle, cell adhesion, signal transduction

Question 30

Knudson’s “two-hit” hypothesis

Answer 30

Two mutations (“hits”) in the genome of a cell required to induce retinoblastoma

Question 31

Genetics of retinoblastoma

Answer 31

In familial cases, child inherits one defective copy of the RB gene, and the other is normal
When normal RB gene undergoes somatic mutation, a tumor develops

Question 32

TP53 overview

Answer 32

Important example of tumor supressor gene
Single most common target for genetic alteration in human tumors
Homozygous loss of TP53 is found in virtually all types of cancer
Mutations that inactivate both copies of the TP53 gene usually in acquired change in somatic cells

Question 33

Where/how does TP53 normally act?

Answer 33

Normally acts in the nucleus to inhibit cell cycle progression
When DNA is damaged, TP53 accumulates, inhibiting cell proliferation and allowing the DNA to repair
If repair mechanisms fail, TP53 activates apoptosis genes

Question 34

Homozygous loss/mutation of TP53

Answer 34

DNA damage goes unrepaired
Mutations become fixed in dividing cells
Leads to uncontrolled cell division: cancer

Question 35

Li-Fraumeni syndrome

Answer 35

Inherited defect of one TP53 allele

25x increased risk for malignancy before age 50