Term
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Definition
| most cancers, means it arises from a single ancestral cell |
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Term
What percent of cancers are hereditable?
What percent have a genetic component? |
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Definition
5-10%
ALL CANCERS have a genetic component |
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Term
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Definition
inhibit cellular proliferation (TSG)
activate cell proliferation (oncognes)
DNA repair genes |
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Term
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Definition
| Inherited (first hit) in a Dominant Form due to a loss of heterozygosity (second hit) |
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Term
| Characteristics of Tumor Cells |
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Definition
Widespread mutations, lots of chromosome breaks and aneuploidy
Hypomethylation of DNA |
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Term
| Breast Cancer Genes with Bad DNA Repair |
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Definition
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Term
|
Definition
| impaired nucleotide excision repair |
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Term
| Hereditary Nonpolyposis Colon Cancer |
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Definition
| DNA mismatch repair genes |
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Term
Aberrant Mitosis
Cohesion Defects
Kinetochose attachment
Mitotic checkpoints |
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Definition
Aberrant Mitosis - multipolar spindles and chromosomes missegregation
Cohesion Defects: premature loss of cohesion between sister chromosomes, or persistant cohesion that won't let go!
Kinetochose attachment - attachment to microtubules form both poles
Mitotic checkpoints: defects here causes chromosome loss |
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Term
| How do tumor cells avoid cellular senescence? |
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Definition
| activation of telomorase! |
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Term
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Definition
| it is a reverse transcriptase, carries its own RNA molecule (kind of a LINE?) |
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Term
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Definition
AD - duh its a cancer!
40% inherited
RB1 gene (TSG with LOH)
Chance of 2nd hit often occurs in more than one cell and affects both eyes
90% penetrance |
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Term
|
Definition
de novo
need to mutate both RB1 gene copies
usually only see it one eye
Seen later in life |
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Term
|
Definition
Initiation, Promotion, Progression Model
Initiation - survival advantage to be able to compete against neighbors
Promotion - adds to ability to outcompete, leading to expansion
Progression - reinforce mutation potential |
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Term
|
Definition
AD
Familial Adenomatous Polyposis
APC (adenomatous polyposis coli gene)
Deletion of normal allele APC w/LOH
*also have activation of KRAS (oncogene) and deletion of p53 |
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Term
| We see LOH in FAPC in what other genes? |
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Definition
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Term
|
Definition
AD -70% penetrance in women
Need LOH
Sporadic breast cancer is rarely from these
Repaid double stranded breaks
BRCA1 is slightly earlier onsent
BRCA2 more male breast cancer |
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Term
|
Definition
Ataxia telangiestasia - XRay sensitivity
Fanconi anemia - sensitivty to cross linkng agents, 13 genes
Xeroderma Pigmentosum -7 forms, pyridimine dimer repair
Bloom Syndrome - POst-Replocation repair error - BLM gene |
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Term
|
Definition
Prostate
Retinoblastoma
Li-Fraumeni - germine mutations in TP53, young age with lots of types of malignancies
Neurofibromatosis Type 1 and 2
Von-Hippel-Lindau
Wilms Tumor
MEN2
Chronic Myeloid Leukemia(Philidelphia chromosome translocation) |
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Term
|
Definition
c-myc 8q24
DNA binding proto-oncogene c-myc ecomes activated by translocation to adjacent immunoglobulin enhancer
MOST COMMON CANCER OF EQUATORIAL AFRICA |
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Term
|
Definition
| look at the cell and especially chromosomes - especially important with Wilm's tumor |
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Term
|
Definition
acute myeloid Leukemia
French-American-British (FAB) classification system
FAB type 2:
t8-21: good response to therapy
t6-9: intermediate outlook
t9-22 (Philly): poor prognosis |
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Term
|
Definition
Acute Lymphoblastic Leukemia
33% translocation
poorer prognosis |
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Term
|
Definition
Chronic Myeloid Leukemia
>90% have Philly choromosome (t9-22) Philly is the new 22
BCR/ABL fusion product
No Philly has worse prognosis |
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Term
|
Definition
likely involved in the initiaition or progression of the neoplasm
Random are likely to be from progression |
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Term
|
Definition
Comparative Genomic Hybridization
detects losses or duplications of whole chromosomes
Mix and expect the yellow (together color)
Gain = red
loss = green
DOES NOT DETECT TRANSLOCATIONS (no loss or gain of material!) |
|
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Term
Resolution of
Karyotying
CGH
Olionucleotides |
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Definition
Karyotying: 5 MB
CGH: 2-3 MB
Olionucleotides: 50 KB |
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Term
|
Definition
| DNA mutations start cancer while epigenetics is likely the promotion of cancer |
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Term
| Hypermethylation of CpG islands |
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Definition
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Term
| Hypomtheylation of entire genome |
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Definition
| leads to genome instability |
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Term
| Colon Cancer and Epigenetics |
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Definition
| MLH1 silenced by methylatin |
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Term
| Acute Leukemia and epigenetics |
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Definition
| recruit histone deacetylases (HDACs) that prevent myeloid differentiation |
|
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Term
| What two environmental chemicals affect DNA methylation and cancer? |
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Definition
Arsenic - does hypomethylation of ras gene
Cadmium - hypometylation by inaivating DNMT1 |
|
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Term
| Histone acetyltransferase vs Histone deactylases |
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Definition
HAT's- transcriptional activators
HDACs - tend to be repressors |
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Term
Histone Modification
Methylation:
Phosphorylation: |
|
Definition
Methylation: lysine methyltransferase and SET domain
Phosphorylation: done to H3S10 and H3S28 needed to have efficient DNA repair |
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Term
|
Definition
Rings of pyrrole joined by methene bridges
Labeled extensively |
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|
Term
substituites for normal porphyrins
Porphyrin III |
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Definition
A-P, A-P, A-P, A-P
III - reversed at IV |
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Term
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Definition
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Term
| Rate limiting reaction of Heme synthesis |
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Definition
AlA Synthase
Requires B6
Takes Glycine and Succinyl CoA to delta-aminolevulinic acid |
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Term
| Regulation of ALA Synthase |
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Definition
inhibited by Heme, feedback inhibition
Reguires B6 (problems w/ tuberculouses drugs)
Hypoxia |
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Term
|
Definition
Takes delta-aminilevulinic acid to porphobilinogen (first pyrrole)
inhibited by heavy metals especially lead (seen by having ALA in urine) |
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Term
| Uroporphrinogen 1 Synthase |
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Definition
Takes Porphobilinogen to Uroporphyrinogen III
if deficient: Acute Intermittent Porphyria |
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Term
| Uroporphrinogen decarboxylase |
|
Definition
converts acetic acid groups to methyl groups
deficiency is porphyria cutanea tarda |
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Term
|
Definition
Adds Fe to protophorphyrin forming Heme
Def is Erythropoietic protoporphyria |
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Term
| Coproporphyrinogen III oxidase |
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Definition
| Coprooporphyrinogen III to protoporphrinogen IX |
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Term
|
Definition
heritable changes with no change to DNA
DNA Methylation
Histone Actylation
RNA interference |
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Term
|
Definition
Usually methylation during gamete formation
Makes monoallelic expression! |
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Term
|
Definition
C and G with a phosphorylated
Alteration in chromatin structure |
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Term
Methylation and Phosphorylation
vs Acetylation |
|
Definition
Tighten the DNA - harder to trasncribe
Loosen the DNA - easier to transcribe |
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Term
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Definition
|
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Term
|
Definition
Gynogeneic - 2 female sets of genes
embryonic tissue ok
Androgeneic - 2 male sets of genes
extra-embryonic tissue OK |
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Term
|
Definition
Gynogeneic - 2 female sets of genes
embryonic tissue ok
Androgeneic - 2 male sets of genes
extra-embryonic tissue OK |
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Term
|
Definition
| no paternal contribution, , benign tumors |
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Term
|
Definition
digynic - grows fetus, no placenta
diandric - grows placenta! |
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Term
|
Definition
| Control the imprinting - dug! |
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Term
|
Definition
| two copies of the same homolog from one parent (whole chromosome is identical) |
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Term
|
Definition
| inheritance of two different homologs from one parent |
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Term
|
Definition
| two chromosomes can have regions of homozygosity and regions of heterozygosity |
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Term
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Definition
| Sperm missing a specific chromsomes fertilizes an egg that has a trisomy for that chromosome |
|
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Term
| PWS vs Anglemans Syndrome |
|
Definition
PWS aint go not father
AS is missing mother allelic expression |
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Term
|
Definition
Gamete Complementation
Trisomy Rescue (could be isodisomy or heterodisomy)
Monosomy Rescue and isochromsome (always isodisomy)
Somatic Recombination |
|
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Term
| Beckwith Wiedeman Syndrome |
|
Definition
IGF2 gene is imprinted with maternal silencing
Activation of maternal IGF2 causes disease
Large Babies, 85% sporadic (somatic in origin)
not a nondisjuction but is a UPD for a chromosome segment |
|
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Term
|
Definition
| Mitotic Recombination causing it |
|
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Term
| UPD and Reciprocal and Robertsonian Translocations |
|
Definition
Recirporcl - VERY rare
Robertsonian - slightly more common, |
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Term
Plasmid
What type of DNA molecules?
What is a vector?
How does a plasmid survive?
What origin of replication does it have? |
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Definition
What type of DNA molecules? Closed circular DNA molecules (CCC)
What is a vector? made of plasmid, can have things added to it
How does a plasmid survive? Use host machine
What origin of replication does it have? OriV |
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Term
|
Definition
F+ and F-
F+ does rolling circle replication from oriT (origin of transfer)
F- becomes F+ |
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Term
|
Definition
| DNA molecules that replicate autonomousl (plasmids, chromosomes, phage) |
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Term
| Origin of replication for a plasmid |
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Definition
|
|
Term
| Broad Host Range Plasmids vs Narrow Host range |
|
Definition
Broad Host Range Plasmids - can survive in multiple hosts, must have lots more proteins required in each environment
Narrow Host range |
|
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Term
|
Definition
binds to iteron sequence @ oriV
series of direct repeats
at low concentration initiates replication |
|
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Term
|
Definition
2 gene operon(parA and parB)
parA and parB join and join to parS which acts as a centromere
Ensures that daughter cells get equal numbers of plasmids |
|
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Term
|
Definition
is made of 2 plasmids as they are sequences that have recombined
broken apart by resolvase |
|
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Term
|
Definition
two versions of the same type of the plasmid cannot co-exist in the same cell
If they are incompatible, this suggests they are related |
|
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Term
| Copy Number vs Incompatability |
|
Definition
Copy Number - Identical chromosome can have mutliple copies
Incompatability - similar plasmids that cannot coexist, will separate upon division |
|
|
Term
|
Definition
viruses that inhabit bacteria
Mostly dsDNA |
|
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Term
|
Definition
virulent or lytic phages - causes lysis
temperate phages - can coexist |
|
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Term
| Why use plaque forming units? |
|
Definition
| Determine the ability of the cirus to infect bacteria |
|
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Term
|
Definition
| integrated DNA into the genome |
|
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Term
|
Definition
Head full packaging, virus picks of host DNA and integrates it into new cells
Can be specialized at attP and attB sites, which are catalyzed by integrates and IHF (integration host factor)
Excision requires exicase (Xis), integrase and IHF |
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Term
|
Definition
Phages that don't lyse the cell
continuously release phages
ssDNA, gram negative bacteria
coliphages are a good example |
|
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Term
| Horizontal / Lateral Gene Transfer |
|
Definition
transfer of genes without sexual reproduction
Phages, plasmids, transposons |
|
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Term
|
Definition
CRE/LoxP
CRE is the recombination
LoxP is the recognition sitesite |
|
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Term
|
Definition
| have a ligand/steriod bind to your similar sequence instead of the correct sequence |
|
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Term
|
Definition
antisense - use 5' region of the NRA and have it make dsRNA
RNA interference -leads to selective degradation of RNA molecule |
|
|
Term
Primary Cell Lines
Transformed Cells
Cancer Cells |
|
Definition
Primary - grab cells from biopsied tissue, these cells easily transformed
Transformed - not cancer but it is immortal
Cancers - from cancer cell line, likely to chance and are genetically unstable |
|
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Term
| Transgenic Overexpression |
|
Definition
Ubiquitous expression - Beta actin promoter
Tissue specific promoster - probasin promoter
Regulated Expression - Stop LoxP, inducible expression |
|
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Term
|
Definition
dsRNA is recognised by DICER (RnaseIII enzyme) and is cleaved into 21023 bp
called siRNA
siRNA are loaded into RISC
siRNA in RISC binds to its completmentary sequence in target mRNA
mRNA is cleaved and degraded by RISC with Endonuclease termed Argonaute |
|
|
Term
| miRNA - endogenous system |
|
Definition
can regulate multiple different mRNA's
make stem loop structures
gets dicer then RISC
2 functions:
1) high degree of homology - degradation
2) low level of homology - translation reduced |
|
|
Term
|
Definition
much more target specific
can be cloned into vectors and plasmids, so they can be stabling expressed in cells and animals
after processing by dicer make specific siRNA's |
|
|
Term
P53 - disease
PTEN - disease
STK11 - Disease |
|
Definition
P53 - Li Fraumeni
PTEN - Cowden
STK11 - Peutz-Jegher |
|
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Term
|
Definition
Digynic - 2 female nucleus, embryo OK, extra tissue fail
Diandric - extra tissue OK, embryo fails |
|
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Term
|
Definition
| allows them to separate upo meiosis |
|
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Term
|
Definition
dsDNA genome, not imcorportated (repeated treatments needed)
35kb of DNA |
|
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Term
|
Definition
ssDNA inserts at chromosome 19
5kb |
|
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Term
|
Definition
| abnormality of biochemical function of a cell |
|
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Term
|
Definition
| nuclear fragmentation - seen in apoptosis |
|
|
Term
| Myocardial Injury detectable enzymes |
|
Definition
| creatine phosphokinase-MB isozyme, lactate dehydrogenase, troponin |
|
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Term
|
Definition
| tissue is brought back to how it was before attack |
|
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Term
|
Definition
| cells near them multiply to replace dead tissue |
|
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Term
|
Definition
| stem cells, divide continuously |
|
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Term
|
Definition
long G0 phase, divde infrequently
hepatocytes, astrocytes, smooth muscle |
|
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Term
|
Definition
cells that do no replicate, neurons, skeleton and cardiac muscle cells
No regeneration, just scar formation |
|
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Term
|
Definition
preparation: clear material, grow granulation tissue (lots of fibroblasts and capillaries)
Produce Fibroneectin- makes capillaries
Collagenization - make collagen from fibroblasts |
|
|
Term
| tropocollagen hydroxylation |
|
Definition
|
|
Term
|
Definition
| breaks down collagen in all scars, even older scars become weaker |
|
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Term
|
Definition
totipotency - give rise to all 3 germs layers and extraembryonic tissue
pluripotency - all 3 germs layers |
|
|
Term
multipotency
oligopotency
unipotency |
|
Definition
multipotency - limited number
oligopotency - only a few
unipotency - only 1 cell type |
|
|
Term
|
Definition
| determine how a stem cell functions |
|
|
Term
| Chrorionic Villus Sampling |
|
Definition
|
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Term
|
Definition
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