Bld 204 Exam 3 Cancer Genetics

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6 Hallmarks of Cancer:

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1. Growth Self Sufficiency
2. Evade Apoptosis
3. Sustained Angiogenesis
4. Limitless Replicative Potential
5. Invade and Metastasize
6. Ignore anti-growth signals

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Two "NEW" Hallmarks:

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1. Reprogramming Energy Metabolism
2. Evading the Immune System

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Of the two "NEW" Hallmarks of cancer,
Reprogramming Energy Metabolism:

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-Aerobic glycolysis (Warburg effect)
-Favored when rapid growth is required

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Of the two "NEW" Hallmarks of cancer,
Evading the Immune System:

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-Most cancer patients are immunocompetent until treatments
-Happens more later

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Carcinogenesis:
The key is ________ Genetic Damage

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NONLETHAL (doesn't kill)

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4 Classes of Regulatory Genes that are targets of genetic damage:

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1. Growth promoting proto-oncogenes
2. Growth inhibiting tumor suppressor genes
3. Genes that regulate apoptosis
4. Genes that are involved in DNA repair

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Oncogenes

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Genes that induce a transformed phenotype when expressed in cells

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Oncogenes are usually mutated or overexpressed versions of

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normal genes - proto-oncogenes

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Dominant

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single allele is sufficient for transformation

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Tumor Suppressor Genes:
Genes that normally...

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Prevent uncontrolled growth

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Tumor Suppressor Genes:
When they are mutated or lost...

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the transformed phenotype appears

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Tumor Suppressor Genes:
Usually, both have to be damaged for phenotype to appear but sometimes a single allele will do it.
This is called?

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HAPLOINSUFFICIENCY

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Tumor Suppressor Genes:
Two types are...

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1. Governors: mutations removes an important "stop" mechanism (RB)
2. Guardians: produce proteins that act as
sensors of genomic damage (p53)

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Genes that are involved in DNA repair may act as

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proto-oncogenes or tumor suppressor genes

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Give an example of a proto-oncogene that
regulates apoptosis

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BCL2

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Genetic Lesions that Lead to Cancer:
Karyotype Changes -

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Changes in the # and appearance of
chromosomes

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Genetic Lesions that Lead to Cancer:
List 3 of these causes

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1. balanced translocations
2. deletions
3. gene amplifications

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Genetic Lesions that Lead to Cancer:
In Balanced Translocation, List the 2 occurences

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1. Translocation moves the gene to where it's under an inappropriate, highly active promoter
(MYC & Burkitt's Lymphoma
Follicular B cell lymphoma & BCL2)
2. Translocation make fusion proteins
(CML & "Philadelphia" chromosome)

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Genetic Lesions that Lead to Cancer:
In Balanced Translocation,
-what are the most common types of cells
-what happens here
-why?

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-Lymphocytes & their precursors
-where genome rearrangements occur
-these cells intentionally make DNA break during antibody or T cell receptor rearrangements

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Genetic Lesions that Lead to Cancer:
Deletion is the...

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2nd most common karyotypic abnormality

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Genetic Lesions that Lead to Cancer:
Large Deletions are more common in

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nonhematopoietic solid tumors

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Genetic Lesions that Lead to Cancer:
Often ______ ______ are deleted

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tumor suppressors

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Genetic Lesions that Lead to Cancer:
Loss of heterozygosity means there's

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-point mutation in one allele
-deletion of the other

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Genetic Lesions that Lead to Cancer:
Gene Amplifications = ?

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proto-oncogenes → (amplification) → oncogenes

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Genetic Lesions that Lead to Cancer:
2 examples of Gene Amplifications

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-NMYC neuroblastoma
-ERBB2 breast cancer

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Genetic Lesions that Lead to Cancer:
Aneuploidy -

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number of chromosomes that is not a multiple of the normal haploid number (23)

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Genetic Lesions that Lead to Cancer:
What occurs during Aneuploidy

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Mitotic checkpoint errors

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Genetic Lesions that Lead to Cancer:
Non-coding single stranded regulatory RNA causes: (2)

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1. ↑ oncogene expression
2. ↓ tumor suppressor expression

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Genetic Lesions that Lead to Cancer:
Epigenetics -

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reversible, heritable changes in gene expression

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Genetic Lesions that Lead to Cancer:
There are no ______ in epigenetics

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mutations

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Genetic Lesions that Lead to Cancer:
In epigenetics, _______ of _______ &
_______ increase expression of genes

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Methylation of histones
and
DNA

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Genetic Lesions that Lead to Cancer:
In Epigenetics, cancer cells have
global ________ of the genome and
________ of certain promotors

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-hypomethylation
-hypermethylation

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Genetic Lesions that Lead to Cancer:
In Epigenetics,
Hypomethylation -

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-silences gene expression
-make the genome unstable & leads to tumor in mice

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Genetic Lesions that Lead to Cancer:
In Selective Pressures,
Multiple genetic alterations =

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transformed phenotype

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Genetic Lesions that Lead to Cancer:
In Selective Pressures,
Tumor Progression -

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is the fact that cancer becomes more malignant with time

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Genetic Lesions that Lead to Cancer:
In Selective Pressures,
Initial tumor is ________
but by the time cancers reach their
dangerous stage,
they may be very _______

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-monoclonal
-heterogenous

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Genetic Lesions that Lead to Cancer:
In Selective Pressures,
tumors undergo ______ _______

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Darwinian Selection

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Genetic Lesions that Lead to Cancer:
What kind of Selective Pressures act on cancer cells?

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-immune
-non-immune

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Genetic Lesions that Lead to Cancer:
Tumors that recur (appear again) are

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-more aggressive
-more resistant (refusal) to treatment