Neoplasia II #6 (1/26/16)

Question 1

What is Metastasis?

Answer 1

The development of secondary deposits of a tumor in a distant site.
*Considered the hallmark of malignancy (but not always seen)

Question 2

In general, the ______ and more _____ a tumor is the more likely it is to metastasize.

Answer 2

Larger and more anaplastic

Question 3

____% of newly diagnosed patients with solid tumors will already have obvious metastases.

Answer 3

30%

Question 4

What are the 3 pathways of Metastasis?

Answer 4

1. Seeding within body cavities - pleura and peritoneum
2. Lymphatic spread - usually seen with carcinomas
3. Hematogenous spread - usually seen with sarcomas, liver and lungs most often affected.

Question 5

Most cancer mortality occurs between ____ and ___ years of age.

Answer 5

55-75

Question 6

What is the proportion of cancer risk that is attributable to environmental sources?

Answer 6

About 2/3rds (65%)

Question 7

Does cancer increase with age?

Answer 7

yes it frequently does…

Question 8

_____% of deaths in children under 15 yrs is due to cancer.

Answer 8

10%

Question 9

What are the 3 broad categories of Genetic predisposition to cancer?

Answer 9

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

Question 10

Inherited cancer syndromes are usually due to what?

Answer 10

A single gene mutation and generally show autosomal dominant transmission. Such as:

• Retinoblastoma
• Familial adenomatous polyposis
• Multiple Endocrine Neoplasia

Question 11

What are some characteristics of Familial cancers?

Answer 11

• Early age onset
• Tumors arising in two or more close relatives
• multiple or bilateral tumors
• Colon, breast, ovary and brain malignancies have been reported to occur in familial patterns.

Question 12

What % of cancers have an identifiable heritable basis?

Answer 12

no more than 5-10%

Question 13

What do Acquired preneopalstic disorders cause?

Answer 13

Increased likelihood of cancer in:

• Persistent regenerative cell replication
• Villous adenomas of the colon
• Leukoplakia of oral or genital mucosa

Question 14

What is Carcinogenesis?

Answer 14

Nonlethal genetic damage, often due to chemicals, radiation, viruses or inherited mutations, is central to all cancers.

Question 15

What 3 classes of Normal regulatory genes are often affected in Carcinogenesis?

Answer 15

Protooncogenes (Growth promoting) , Cancer suppressor (growth inhibiting) genes, apoptosis genes.

Question 16

How do DNA repair genes contribute to cancer development?

Answer 16

They indirectly contribute to cancer development since acquired mutations can be repaired.

Question 17

T or F, Cancer is a multistep process at both the phenotypic and genetic levels.

Answer 17

True

Question 18

What is the difference between Prooncogenes and oncogenes?

Answer 18

Prooncogenes are normal functional components of the cell.

Oncogenes encode proteins called oncoproteins that while similar to prooncogene products they lack regulation.

Question 19

Prooncogenes are transformed to oncogenes by: (2 things)

Answer 19

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 protein.
   * This activates oncogenes

Question 20

All normal cells require ___ stimulation to undergo proliferation.

Answer 20

Growth factor

Question 21

What does mutation or over expression of Growth factor cause?

Answer 21

It may deliver continuous mitogenic signals and overexertion can make cancer cells which are hyper responsive to even normal levels of GF.

Question 22

Approx. ____% of all human tumors contain mutated ______.

Answer 22

RAS oncogene

Question 23

How does Mutant RAS behave differently than good old fashioned RAS?

Answer 23

RAS is normally inactivated quickly, yet mutant RAS remains in its active form stimulation CONSTANT cell proliferation.

Question 24

In regards to nuclear transcription factors, which gene is most commonly affected?

Answer 24

MYC

Question 25

What does MYC gene dysregulation cause?

Answer 25

Continuous activation of cyclin-dependant kinases (CDK’s) driving cell to divide.

Question 26

______ also represses CDK inhibitors.

Answer 26

MYC

Question 27

CDK’s are regulated by ________.

Answer 27

2 families of CDK inhibitors

Question 28

What does the product of the RB gene do?

Answer 28

Regulates transcription

Question 29

What is Knudson’s “Two Hit” hypothesis?

Answer 29

That two mutations “hits” in the genome of a cell are required to induce retinoblastoma.

Question 30

For retinoblastoma to occur, what must happen?

Answer 30

Both normal alleles of the RB locus must be inactivated (2 hits)

Question 31

In familial cases, child inherits one _______ of the RB gene and the other Allele is ______.

Answer 31

One defective copy and the other allele is normal.

* When normal RB gene undergoes somatic mutation, tumor develops.

Question 32

____ is the single most common target for Genetic alterations in human tumors.

Answer 32

TP53

*Homozygous loss of TP53 is found in almost every type of cancer.

Question 33

Mutations that inactivate both copies of the TP53 gene usually are an __________.

Answer 33

Acquired change in somatic cells

Question 34

What does TP53 normally do?

Answer 34

It normally acts in the Nucleus to inhabit cell cycle progression.

• When DNA is damaged TP53 accumulates and inhibits cell proliferation and allows time for DNA to repair.
• If repair fails, TP53 activates “cell suicide” apoptosis genes.

Question 35

What happens with homozygous loss or mutation of TP53?

Answer 35

Your DNA damage will go on unprepared.
These mutations become permanent in diving cells.
Leads to uncontrolled cell division = cancer.

Question 36

What is Li-Fraumeni syndrome?

Answer 36

Inherited defect of one TP53 allele = 25X more risk of malignancy before age 50.