10-28: Oncogenes and Tumor Suppressors Flashcards
Chromosomal translocation
Chronic Myeloid/Myelogenous Leukemia (CML)
- 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
Blood cell development
How are granulocytes formed?
Myloid stem cell -> myeloblast -> granulocytes
granulocytes= eosinophil, basophil, neutrophil
Cancer genetics
Most inherited mutations associated with
cancer affect a person’s __________: increase for developing a certain cancer
Risk
A single mutation is not usually enough to cause cancer, but could increase the risk
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.
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.
Tumor cells can arise from
What are two ways that tumors form?
- increased cell division, normal apoptosis
- Normal cell division, decreased apoptosis
Epigenetic/genetic gene changes
What type of inactivation occurs when an accident causes packaging into heterochromatin?
Epigenetic gene inactivation
Epigenetic/genetic gene changes
What type of inactivation occurs when an accident causes methylation of C nucleotides?
Epigenetic gene inactivation
Epigenetic/genetic gene changes
What type of inactivation occurs when a nucleotide is accidentally changed?
genetic
Types of cancers
Malignant tumors are classified according to
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)
Benign vs Malignant Tumors
What causes a benign tumor to become malignant?
When it travels outside of the basal lamina (travels outside of localized area)
Cancer stem cells
What are Transit-amplifying cells?
Group of undifferentiated cells that act as a bridge between stem cells (SCs) and differentiated cells
Cancer Stem cells
What are Cancer Stem Cells? (3 functions)
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
Cancer stem cells
Cancer stem cells generally divide more ______.
Slowly
May survive radiation and or chemo as these treatments are targeted for rapidly dividing cells
Angiogenesis and Tumors
Why do tumors secrete angiogenic signals?
Supply the nutrient needs and growth factors of the growing tumor
Angiogenesis and Tumors
What is a consequence of tumor angiogenesis?
metastasis can colonize distant sites
What are some properties contributing to cancerous growth?
- 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
Cancer genes
Classification of cancer genes: (3)
– Genes that normally inhibit cellular proliferation
– Genes that activate proliferation
– Genes that participate in DNA repair
Oncogenes and Tumor Suppressors
What are mutated proto-oncogenes?
Oncogenes
Proto-oncogenes cause cell growth and division. When they are mutated, they activate when they should not be activated= oncogenes
Oncogenes and Tumor Suppressors
What happens when a tumor suppressor gene is mutated?
- 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
proto-oncogenes cause cancer when they are
ACTIVATED
Proto-oncogenes –ACTIVATED–> oncogenes
tumor suppression genes cause cancer when they are
INACTIVATED
When tumor suppressors are inactivated, they can not suppress tumors
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?
**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
Retinoblastoma (Rb) Protein and Cell Cycle Control
When Rb is active, it is bound to
E2F (a transcription regulator)
When Rb is innactivated, what happens?
E2F is activated, causing DNA synthesis
