HTHSCI 1DT3 Lecture Notes - Lecture 22: Carmustine, Platelet-Derived Growth Factor Receptor, Anaplasia
23 Jun 2018
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When Good Cells Go Bad – Cancer
12th October 2012
Discuss the origins of cancer
Understand the difference between genetic and epigenetic mutations!
List and discuss the hallmarks of cancer!
Discuss the differences between oncogenes and tumour suppressor genes
Describe glioma classification!List the frequently altered pathways in Glioblastoma
Cancer: Umbrella term covering a plethora of conditions characterized by unscheduled and uncontrolled
cellular proliferation.
Cancer Groups:
Carcinoma: Cancer that begins in the skin or in the tissues that line or cover internal organs.
Sarcoma: Cancer that begins in the bone, cartilage, fat, muscle, blood vessel, or other connective or
supportive tissue.
Leukaemia: Cancer that starts in blood forming tissues such as the bone marrow and causes large
numbers of abnormal blood cells to be produced and enter the blood.
Lymphoma and Myeloma: Cancers that begin in the cells of the immune system.
Central Nervous System Cancers: Cancers that begin in the tissues of the brain and spinal cord.
Origins of Cancer:
Accumulation of mutations in genes:
Genetic: Changes in DNA Sequence
Epigenetic:
Heritable changes in gene expression that occur without a change in DNA
sequence.
Epigenetic mechanisms provide an ‘extra’ layer of transcriptional control that
regulates how genes are expressed.
Critical components in the normal development and growth of cells.
Epigenomic profiles can be used as cancer cell markers and markers of tumour
prognosis.
Derailiing a wide spectrum of regulatory and downstream effector pathways.
Epigenetic Modification:
Aberrant cytosine methylation observed in many cancers
Methylation profiling can identify distinct subtypes of cancers.
Useful in predicting the clinical properties of cancers in individual patients including sensitivity to
anticancer agents.
Methylation patterns may shed light on the pathways involved in pathogenesis.
Origins of Cancer:
Depending on how they affect each process, these genes can be grouped into two general
categories:
Tumour Suppressor Genes (TSG)
Normal genes that slow down cell division, repair DNA mistakes and promote
apoptosis.
Cause cancer when they are inactivate
Abnormalities can be inherited as well as acquired.
Oncogenes
Result from the activation of proto-oncogenes
Most develop from mutations in normal genes (proto-oncogenes)
Acquired mutations.
Hallmarks of Cancer:
Self sufficiency in growth signals
Insensitivity to growth inhibitory signal
Evasion of apoptosis
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Evasion of apoptosis
Limitless replicative potential
Sustained angiogenesis
Tissue invasion and metastasis.
Douglas Hanahan , Robert A. Weinberg
Hallmarks of Cancer
Cell Volume 144, Issue 5 2011 646 - 674
1. Self sufficiency in growth signals
2. Insensitivity to growth inhibitory signals
3. Evasion of apoptosis
4. Limitless replicative potential
5. Sustained angiogenesis
6. Tissue invasion and metastasis
Parallel Pathways of Tumourigenesis
Douglas Hanahan , Robert A Weinberg Cell Volume 100, Issue 1 2000 57 - 70
Parallel Pathways of Tumorigenesis
Hallmark 1: Self-sufficiency in Growth Signals
Ability to maintain growth irrespective of extracellular growth signal changes (or reduction?)
Hallmark 1:
self sufficiency in growth signals
Normal cells
quiescent state active proliferative state
Growth signals
Types of proteins encodes by oncogenes
Many oncogenes mimic normal growth signals
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Hallmark 1:
self sufficiency in growth signals
Normal cells
quiescent state active proliferative state
Growth signals
Types of proteins encodes by oncogenes
Many oncogenes mimic normal growth signals
Mechanisms of oncogene activation
Hallmark 2: Insensitivity to Negative Signals
Inactivating mutations in Tumour Suppressor Genes:
Point mutations
Chromosome deletions
LOH
Altered methylation of promoters – epigenetics
Classic RB Gene:
Germline mutations in RB and one acquired somatic mutation leads to retinoblastoma
80% of small cell lung cancer have an RB mutation
P53 – 50-73% of all cancers have a p53 mutation (loss both or dominant negative).
Hallmark 3: Evasion of Apoptosis
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Document Summary
Understand the difference between genetic and epigenetic mutations. Discuss the differences between oncogenes and tumour suppressor genes. Describe glioma classification list the frequently altered pathways in glioblastoma. Cancer: umbrella term covering a plethora of conditions characterized by unscheduled and uncontrolled cellular proliferation. Carcinoma: cancer that begins in the skin or in the tissues that line or cover internal organs. Sarcoma: cancer that begins in the bone, cartilage, fat, muscle, blood vessel, or other connective or supportive tissue. Leukaemia: cancer that starts in blood forming tissues such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and myeloma: cancers that begin in the cells of the immune system. Central nervous system cancers: cancers that begin in the tissues of the brain and spinal cord. Heritable changes in gene expression that occur without a change in dna sequence.
