Cancer Genetics and Genomics Flashcards Preview

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Flashcards in Cancer Genetics and Genomics Deck (20):

Clonal disorder

All cells in a tumor arise from a single cell whose growth control has gone wrong


Properties of Malignant Cells

Grow more rapidly than normal cells of the same origin
Fail to exhibit normal cell-cell interactions


Multi-hit hypothesis

Numerous genetic abnormalities must accumulate to promote the evolution of a tumor



Genes that encode proteins that are integral for the normal growth of the cell, particularly those involved in cell-cell interactions, cell cycle, and signal transduction



Genes that have undergone mutations such that the proteins they encode no longer function appropriately in the cell --> unregulated cell growth and proliferation



Used for treatment of chronic myelogenous leukemia b/c of its ability to selectively inactivate the ber-abl fusion kinase but not the normal abl kinase


Result of a gain-in-function mutation?

B/c gain-of-function mutations that interfere with proper regulation of proto-oncogenic activities or that amplify the # of copies of proto oncogenes can lead to disregulation of the oncogenic activity


Why do oncogenes act in a dominant fashion at the cellular level?

Only one of the 2 genes homologs needs to be defective in order for the protein to cause problems in the physiology of the cell


Proteins encoded by oncogenes?

growth factors, growth factor receptors, signal transduction molecules, nuclear transcription (same as proto-oncogenes)



miRNA molecules that are responsible for the post-transcriptional regulation of upwards of 200 unique genetic targets per miRNA gene

Some the miRNAs act as oncogenes and inhibit large numbers of tumor suppressor genes


Tumor suppressor genes

Genes that encode proteins whose normal physiological role is largely to prevent the rampant proliferation of cells

are loss-of-function mutations that act in a recessive fashion at the cellular level
*both copies of the tumor suppressor gene must be inactivated in order for tumorigenesis to occur


Caretaker genes

Tumor suppressors

DNA repair genes


Gatekeeper genes

Tumor suppressors

Cell cycle checkpoint genes


Xeroderma Pigmentosum

Mutation in genes required for nucleotide excision repair
Sensitive to UV radiation

*recessive chromosome instability syndrome*


Ataxia Telangiectasia

ATM mutation prevents proper DNA damage repair for double stranded breaks

Presence of DNA free ends generates a highly unstable genomic state and these fusogenic ends often associate to create new translocations

Karyotype: long chromosome with many constriction points
*recessive chromosome instability syndrome*


Fanconi Anemia

Patients harbor genetic lesions in proteins that interact with ATM
Also acutely sensitive to agents that cause double-stranded breaks

Symptoms: bone marrow failure

*recessive chromosome instability syndrome*


Bloom Syndrome

Mutations in another protein complex that interacts with ATM and Fanconi patients

Symptoms: repeated otitis media and pneumonia, early menopause, a wide variety of cancer susceptibilities

*recessive chromosome instability syndrome*


RB1- 2 hit hypothesis

Both copies of RB1 must be inactivated to promote tumor development

*incomplete penetrance b/c some people with the predisposition of rb do not end up getting the tumor even though high chance that it you have 1 mutated copy, the other will also be mutated


Tumor suppressor- familial inheritance

Inherited in apparent dominant fashion


Loss of heterozygosity

Acquiring a hereditary mutation in a tumor suppressor predisposes an individual to these effects

Heterozygous individuals have a higher likelihood of acquiring a mutation (ie: deletion) in the single remaining wild type allele of the gene

ie: p53- Li Fraumeni syndrome