10-28: Oncogenes and Tumor Suppressors

Question 1

Chromosomal translocation

Chronic Myeloid/Myelogenous Leukemia (CML)

Answer 1

• Bone marrow produces excessive amounts of abnormal granulocytes
• fusion of the BCR and ABL genes

• Bone marrow produces
  excessive amounts of abnormal
  granulocytes at the expense of
  the other healthy white blood
  cells.
• Pieces of chromosomes 9 and 22
  break off and trade places,
  resulting in a fusion of the BCR
  and ABL genes.
• This translocation creates a new
  chromosome called the
  Philadelphia (Ph) chromosome. * It’s rare in children and typically
  occurs in adults during or after
  middle age

Question 2

Blood cell development

How are granulocytes formed?

Answer 2

Myloid stem cell -> myeloblast -> granulocytes

granulocytes= eosinophil, basophil, neutrophil

Question 3

Cancer genetics

Most inherited mutations associated with
cancer affect a person’s __________: increase for developing a certain cancer

Answer 3

Risk

A single mutation is not usually enough to cause cancer, but could increase the risk

Question 4

Tumor growth and progression
generally involves multiple, successive
rounds of genetic changes with the end
result of __________________ selection of a ___________
cell that produces a tumor or cancer.

Answer 4

Natural, clonal

Tumor growth and progression
generally involves multiple, successive
rounds of genetic changes with the end
result of natural selection of a clonal
cell that produces a tumor or cancer.

Question 5

Tumor cells can arise from

What are two ways that tumors form?

Answer 5

1. increased cell division, normal apoptosis
2. Normal cell division, decreased apoptosis

Question 6

Epigenetic/genetic gene changes

What type of inactivation occurs when an accident causes packaging into heterochromatin?

Answer 6

Epigenetic gene inactivation

Question 7

Epigenetic/genetic gene changes

What type of inactivation occurs when an accident causes methylation of C nucleotides?

Answer 7

Epigenetic gene inactivation

Question 8

Epigenetic/genetic gene changes

What type of inactivation occurs when a nucleotide is accidentally changed?

Answer 8

genetic

Question 9

Types of cancers

Malignant tumors are classified according to

Answer 9

the tissue or cell type from which they originated

– Carcinomas are cancers arising from epithelial cells
– Sarcomas arise from connective tissue or muscle cells
– Leukemias derive from white blood cells and their
precursors (hematopoietic cells) – Lymphomas derive from lymphatic tissue – Gliomas derive from the glial cells of the central nervous
system (CNS)

Question 10

Benign vs Malignant Tumors

What causes a benign tumor to become malignant?

Answer 10

When it travels outside of the basal lamina (travels outside of localized area)

Question 11

Cancer stem cells

What are Transit-amplifying cells?

Answer 11

Group of undifferentiated cells that act as a bridge between stem cells (SCs) and differentiated cells

Question 12

Cancer Stem cells

What are Cancer Stem Cells? (3 functions)

Answer 12

a small population of cells within a tumor that have the ability to
1. self-renew
2. initiate tumors
3. give rise to more differentiated cells

Question 13

Cancer stem cells

Cancer stem cells generally divide more ______.

Answer 13

Slowly

May survive radiation and or chemo as these treatments are targeted for rapidly dividing cells

Question 14

Angiogenesis and Tumors

Why do tumors secrete angiogenic signals?

Answer 14

Supply the nutrient needs and growth factors of the growing tumor

Question 15

Angiogenesis and Tumors

What is a consequence of tumor angiogenesis?

Answer 15

metastasis can colonize distant sites

Question 16

What are some properties contributing to cancerous growth?

Answer 16

• Cancer cells are relatively insensitive to anti-proliferative
  extracellular signals
• Cancer cells induce help from normal stromal cells in their
  microenvironment
• Cancer cells are genetically unstable
• Cancer cells produce telomerase or acquire another means of
  stabilizing their telomeres

Question 17

Cancer genes

Classification of cancer genes: (3)

Answer 17

– Genes that normally inhibit cellular proliferation
– Genes that activate proliferation
– Genes that participate in DNA repair

Question 18

Oncogenes and Tumor Suppressors

What are mutated proto-oncogenes?

Answer 18

Oncogenes

Proto-oncogenes cause cell growth and division. When they are mutated, they activate when they should not be activated= oncogenes

Question 19

Oncogenes and Tumor Suppressors

What happens when a tumor suppressor gene is mutated?

Answer 19

• The normal function of the gene is to slow down cell division, so when they are mutated they cannot do this.
• Mistakes will not be repaired and apoptosis does not occur

Question 20

proto-oncogenes cause cancer when they are

Answer 20

ACTIVATED

Proto-oncogenes –ACTIVATED–> oncogenes

Question 21

tumor suppression genes cause cancer when they are

Answer 21

INACTIVATED

When tumor suppressors are inactivated, they can not suppress tumors

Question 22

Alfred Knudson: the 2-Hit Hypothesis of Retinoblastoma

Knudson’s original hypothesis was that a person needed to acquire
how many copies of the Rb gene?

Answer 22

**TWO copies of the Rb gene
**
- Hereditary retinoblastoma: The first mutation, or “hit”, occurs in the
germline, and the second hit occurs in a somatic cell.
– Nonhereditary retinoblastoma: Both hits occur in a somatic cell

Question 23

Retinoblastoma (Rb) Protein and Cell Cycle Control

When Rb is active, it is bound to

Answer 23

E2F (a transcription regulator)

Question 24

When Rb is innactivated, what happens?

Answer 24

E2F is activated, causing DNA synthesis