Lecture 5: Mutation and Cancer Flashcards
Gene Mutations Classification:
- mutations are inherited from a parent and are present throughout a person’s life in virtually every cell in the body
Inherited (germ line)
-These mutations are also called germline mutations because they are present in the parent’s egg or sperm cells, which are also called germ cells
Gene Mutations Classification:
- mutations occur at some time during a person’s life
- present only in certain cells, not in every cell in the body.
- These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division.
Acquired (somatic/sporatic)
Can genetic mutations in somatic cells (cells other than sperm or egg cells) be passed on the next generation?
No
What are the types of mutations at the chromosomal level?
- Deletions
- Duplications
- Inversions
- Translocations t[#,#]
d9p
Acute Lymphoblastic Leukemia
d13q14
Retinoblastoma
Rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common malignant cancer of the eye in children.
Retinoblastoma
Philadelphia Chromosome-
t(9:22)
Chronic Myelogenous Leukemia(CML)
most common variant: t(8;14)(q24;q32)
Burkitts Lymphoma
______ encodes a cytoplasmic tyrosine kinase
C-abl
____ promotes oligomerization
Bcr
________ fusion promotes activation of abl by oligomerization induced autophosphorylation.
Bcr-abl
Philadelphia chromosome –
translocation of chr ____ and ____
9, 22
-Translocation resulting in fusion of 2 genes with alters structure of normal c-abl protein
Burkitts Lymphoma-most Common Variant
T….
(8;14)(q24;q32)
Burkitts Lymphoma-most Common Variant
T(8;14)(q24;q32):
____ is brought under the
transcriptional control of the IG enhancer elements leading to its constitutive transcriptional deregulation.
MYC
Associated with the Epstein-Barr Virus (EBV) in nearly 100% of cases in endemic form in central Africa.
Burkitts Lymphoma
Burkitts Lymphoma:
In the sporadic forms (occur in Western countries), EBV is present in approximately ___% of cases and in ____% of immunodeficiency associated cases
30, 40
Type of mutation at the DNA level.
- transition (purine for purine, pyrimidine for pyrimidine)
- transversion (purine for pyrimidine)
Base substitutions (Point Mutation)
Mutation type at the DNA level leads to risk factor and/or risk marker in
disease
SNP
Type of mutations at the DNA level
- Base substitutions (Point Mutation)
- Frame shift mutation
- Deletion
- Insertion
- SNP (when leads to risk factor and/or risk marker in
disease)
Consequences Of Point Mutations
-Silent
-Missense*
-Nonsense-change to stop codon
Examples of Missense point mutation
hemaglobinopathies (sickle cell, T for A; glutamic acid to
valine)
Examples of nonsens-change to stop codon mutations
- Alpha thalassemias
-decreased protein produced (alpha vs beta globin)
-Constant Spring: from stop codon to glutamine @ 142 (TAA to
CAA) in alpha-thalassemia
from stop codon to glutamine @ 142 (TAA to
CAA) in alpha-thalassemia
Constant Spring
Fragile X: FMR-1(fragile -X mental retardation protein:
Premutation alleles generally considered to be between ____ to ____ repeats in length.
55, 200
Fragile X: FMR-1(fragile -X mental retardation protein:
Excessive amplification of a base triplet normally repeated only a few to 50 times, most commonly in the _____________.
5’ untranslated region of FMR1
Fragile X: FMR-1(fragile -X mental retardation protein:
Fragile X: FMR-1(fragile -X mental retardation protein: > _____ repeats of CGG)
200
Huntingtons Disease
Caused by the length of a repeated section (____, codes for _____) of a gene exceeding a normal range.
CAG, Gin
Huntington’s Disease:
The HTT gene is located at ________.
4p16.3
> 40 trinucleotide repeats – full penetrance ie. the proportion of individuals carrying a particular variant of a gene (allele or genotype) that also expresses an associated trait (phenotype)
Huntington’s Disease
Epstein-Barr virus, one of the herpes viruses:
Burkitt’s Lymphoma-involves the fusion of
c-myc, IGH
Epstein-Barr virus:
Causes infectious mononucleosis and linked to what two cancers?
non-Hodgkin lymphomas and nasopharyngeal cancer.
The cancer is thought to be due to the pro-oncogenic effect of viral DNA
incorporated into host lymphocyte DNA
Human T-cell Leukemia (HTLV-1)
Long-standing infection with the hepatitis ___ or ____ viruses can lead to cancer of the liver
B, C
The Kaposi’s sarcoma-associated herpesvirus (KSHV), is associated with
non-Hodgkin lymphoma