Shared Flashcard Set

Details

C4-29C Cancer genetics/ chromo. abnormalities I
p53 is def going to be on one of these cards
12
Immunology
Professional
12/11/2010

Additional Immunology Flashcards

 


 

Cards

Term




Risk Factors for Prostate Cancer

Definition

Age

Family History

Ethnicity

Dietary fat intake

Smoking

Term




Familial cancers

Definition

Hallmarks:
Early age of onset
Bilateral
More aggressive phenotype
individuals share inherited susceptibility genes

Term




Susceptibility is inherited

Definition

-Susceptibility is inherited as a dominant trait

-Many affected in the family, but accounts for few cases (<10%) compared with sporadic cancers from the same tissue

Term




Different genetic alterations may coincide with increasing progression of disease

Definition

Colon:

 

-RAS Activation

-APC Loss

-HNPCC Mutation

-later loss of p53

 

Prostate:

 

-8p deletion

-PTEN loss

 

much later, loss of p53 and 8q amplification

Term

 

 

 

Solid tumors:

Definition

Solid tumors:

characterized by high number of random and non-random genomic deletions, amplifications and rearrangements

Few have diagnostic single defect or diagnostic or causative translocations; PROSTATE IS AN EXCEPTION!
Heterogeneous temporally, spacially, genetically
Highly variable pattern of gene expression

Term




Generation of clonal cancers

Definition

If block occurs in differentiation, all progeny will be blocked at that stage

 

Proliferation (and decreased rate of death) of “early” stage cells are the cells of the hematopoeitic cancer

Term




CML: Chronic Myeloid Leukemia

Definition

Ph. Chromosome
BCR-ABL gene – “210” protein

6000 (US) develop CML each year

risk increases after age 50

2x more prevalent in men compared to women
3 phases: chronic, accelerated,

blast crisis


Term




The Philadelphia chromosome

Definition

-Diagnostic cytogenetic lesion in ~95% of Chronic Myelogenous Leukemia and 20% of ALL

 

Seen by eye (at microscope) in ~80% of CML cases by cytogenetics

The other 20% were almost all positive for translocation by molecular testing

Term



Making use of the known molecular mechanism: Philadelphia positive CML refractory to conventional therapy

Definition

A good, rationally designed therapy is specific for the defect involved; general metabolic poisons have low benefit relative to side effects

Needs to differentiate between affected cells and normal cells

New class of activated tyrosine kinase inhibitors  recently developed

Term




STI-571: A rational drug designed from understanding basic science

Definition

STI-571 is marketed as Gleevec

 

Increased potency and efficiency of binding to activated receptor tyrosine kinase, specifically BCR-ABL, PDGF, and c-kit

Effective in treating CML and ALL with Ph+ chromosome

Effective in treating gastrointestinal stromal tumors (most are c-kit positive)

 

Appears to selectively induce differentiation and apoptosis of cells with the BCR-ABL (or c-kit) mutations; patients achieve a “cytogenetic remission”

 

Phase I trials for CML and ALL began in June 1998

Some complete remissions were achieved

Most effective against early disease

Affects progression, not survival long term

Trials to determine how to use Gleevec to affect survival are underway

Term

 

 

 

Balanced translocations and solid tumors

Definition

Balanced translocations and gene fusions also occur in some solid tumors and are associated with progression and outcome

Term

 

 

 

Cancer genetics facts

Definition

Cancer can be familial or sporadic
List the differences in presentation between familial and sporadic tumors
Tumors may preferentially metastasize to certain sites; probably genetically determined
Tumors form because normal gene expression patterns are disrupted
Gain or loss of function due to deletion, amplification, or mutation
Tumors can be big or small, focal or not
Solid tumors may have a gene fusion similar to hematopoeitic malignancies, but likely also have a plethora of other molecular changes
The molecular mechanism can be used to develop therapeutics, diagnostics, predict recurrence

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