BI203 Lecture 25: Cancer

Question 1

Cancer arises from a(n) ___of genetic changes (mutations).
Most cancers have a minimum of ___ to ___ different mutated genes.
Not a hereditary disease – we do not pass on cancer to offspring.
We can inherit dispositions (susceptibility) to cancer.
Many genes that are mutated in cancer are involved in regulating the cell cycle.

Answer 1

accumulation, 6 to 9

Question 2

___ - Malignancies of epithelial cells (about 90% of human cancers).

Answer 2

Carcinomas

Question 3

___ - Solid tumors of connective tissue such as muscle, bone, cartilage, and fibrous tissue (rare in humans).

Answer 3

Sarcomas

Question 4

___ and ___ arise from the blood-forming cells and immune system cells, respectively.

Answer 4

Leukemias, Lymphomas

Question 5

The four most common cancers are ___, ___, ___ and ___.

___ cancer, by far the most lethal, is responsible for nearly 30% of all cancer deaths.

Answer 5

breast, lung, prostate, colon

lung

Question 6

A fundamental feature of cancer is ___ ___ - tumors develop from single cells that begin to proliferate abnormally.

The single-cell origin has been demonstrated by analysis of X chromosome inactivation patterns.

Answer 6

tumor clonality

Question 7

___ ___ - Mutation leads to abnormal proliferation of a single cell, which grows into a population of clonal tumor cells.

Answer 7

tumor initiation

Question 8

___ ___ - Additional mutations occur within cells of the tumor population.

Answer 8

tumor progression

Question 9

___ ___ - Descendants of these cells become dominant.

Answer 9

clonal selection

Question 10

___ or ___ - A small benign neoplasm.

Answer 10

adenoma, polyp

Question 11

___ -> malignant -> ___

Answer 11

benign -> malignant -> metastatic

Question 12

benign -> ___ -> metastatic

Answer 12

benign -> malignant -> metastatic

Question 13

Hematopoietic cells are maintained by the proliferation

and ___ of hematopoietic stem cells.

Answer 13

differentiation

Question 14

All types of blood cells are derived from stem cells in the bone marrow. Once they are fully differentiated, cell division ceases.

___ cells don’t undergo terminal differentiation; they are arrested at early stages and retain the capacity for proliferation.

Answer 14

Leukemic

Question 15

There are ___ general causes for Cancer.

Answer 15

3

Question 16

The 3 general causes for Cancer:

Answer 16

1) Mutations in critical regulatory genes
2) Chemicals that promote tumors by increasing cell proliferation
3) Tumor viruses

Question 17

1) Mutations in critical regulatory genes:
- Mutations that occur during ___, for example via:

• ___ ___ (e.g., cigarette smoke)
  > causes 90% of all lung cancers and 1/3 of all cancer deaths
• ___ (e.g., UV irradiation from the sun)

Answer 17

life, chemical carcinogens, radiation

Question 18

2) Chemicals that promote tumors by increasing cell proliferation:
- i.e. ___ links to breast and endometrial cancers

Answer 18

estrogen

Question 19

3) Tumor viruses:

- ___ to ___% of human cancers

Answer 19

10 to 20%

Question 20

Studies of ___ ___ ___ (RSV) led to identification of the first viral oncogene.
___ ___ ___ (RSV) transformed chicken embryo fibroblasts in culture and induces sarcomas.

Answer 20

rous sarcoma virus (RSV)

Question 21

The closely related avian leukosis virus (ALV) replicates in the same cells without inducing ___.
This suggested that RSV contains specific genetic information for ___.

Answer 21

transformation

Question 22

___ - A gene that has the potential to cause cancer.

In tumor cells, they are often mutated or expressed at high levels.

Answer 22

oncogene

Question 23

___ - A normal gene that can become an oncogene due to mutations or increased expression.
Ex: Ras, Wnt, Myc and ERK.

Answer 23

proto-oncogene

Question 24

___ ___ - A gene that protects a cell from one step on the path to cancer.
Ex: Rb, p53, BRCA1 and BRCA2.

Answer 24

tumor suppressors

Question 25

Many oncogenes encode components of signaling pathways that stimulate cell ___.

Answer 25

proliferation

Question 26

The first human oncogene identified was the homolog of the ____ oncogene of Harvey sarcoma virus. Three members of the ___ gene family (rasH, rasK, and rasN) are the oncogenes most frequently encountered in human tumors.

Answer 26

rasH, ras

Question 27

A point mutation of ___ to ___ converted the normal ras gene (proto-oncogene) into an oncogene. These specific ras mutations are caused by chemical carcinogens.

Answer 27

glycine to valine

Question 28

ras genes encode guanine-binding proteins that function in transduction of mitogenic signals from many growth factor receptors. Ras proteins alternate between ___ (GTP-bound) and ___ (GDP-bound) states.

Answer 28

active, inactive

Question 29

Oncogenic mutations in ___ ___ pathway proteins can promote abnormal cell survival.

Answer 29

PI 3-kinase

Question 30

The ___ ___ increases expression of Bcl-2, which blocks apoptosis.

Answer 30

Bcl-2 oncogene

Question 31

___ both inhibits cell proliferation & induces apoptosis. Mutations which INACTIVATE ___ are commonly found in several forms of cancer

Answer 31

p53

Question 32

Mutations of p53 play a role in about ___% of all cancers.

Answer 32

50%

Question 33

BRCA1 and BRCA2 genes (responsible for some inherited breast and ovarian cancers) are ___ __ which maintain the integrity of the genome. Mutations and inactivation of stability genes leads to high mutation frequency in oncogenes or tumor suppressor genes.

Answer 33

stability genes

Question 34

There are ___ different mechanisms of oncogene activation.

Answer 34

3

Question 35

The 3 different mechanisms of oncogene activation:

Answer 35

point mutation, DNA rearrangement, DNA amplification

Question 36

___ ___ OR ___ ___ - Increases activity of the protein.

Answer 36

point mutation, DNA amplification

Question 37

___ ___ - Increases activity and/or expression of the protein.

Answer 37

DNA rearrangement

Question 38

The receptor for platelet-derived growth factor (PDGFR) is converted to an oncogene by a chromosome translocation and replacement of the amino terminus by a transcription factor called ___. ___ sequences of the ___/___ fusion protein dimerize in the absence of growth factor binding. Result: ___ is ___ ___.

Answer 38

Tel, Tel, Tel/PDGFR, kinase is continuously active

Question 39

The Bcl-2 oncogene is due to a ___ ___ in B-cell lymphomas.

Answer 39

DNA rearrangement

Question 40

An example of DNA amplification creating an oncogene: ___ in breast and ovarian cancer.

Answer 40

ErbB-2

Question 41

The oncogene ErbB-2 in breast and ovarian cancer is a result of a ___ ___.

Answer 41

DNA amplification