Lectures 15&16: Cancer Genetics Flashcards
Uncontrolled cell growth char’d by a change in the normal organizational pattern of tissues or cells, including karyotypic changes and metastasis.
Malignancy
Malignant tumor of potentially unlimited growth that expands locally by invasion and systemically by metastasis.
Cancer
Sarcoma is to mesenchymal tissue (bone, cartilage, muscle, fat) as carcinoma is to ??
Epitheloid tissue
Leukemia affect WBCs from the bone marrow, while lymphomas affect WBCs from the the ??
Spleen and lymph nodes.
Cancer most likely results from a combination of what two effects?
Environmental and cellular effects.
List hallmarks of cancer
- Mutation or loss of genes involved in cell control including control of growth/division, prolif, metab
- Env elmnts may influence mutation
- Mutations may be inherited or acquired
- Chromosome instability (CIN; gain, loss, or rearr of chrom’s or breakage)
Structurally important “housekeeping” genes involved in cell proliferation and development are called? Name some general examples of what they meddle in.
Proto-oncogenes. Examples include growth factors, cell surface receptors, intracellular signal transduction, DNA binding proteins (txn), reg of cell cycle.
Gain of function mutations in proto-oncogenes (could be a translo, point mut, amplification) are necessary recessive, requiring two mutations to lead to tumorigenesis. T or F?
False. Dominant - requires 1 hit.
A translocation betw C 9 and 22, resulting in a fusion of a proto-oncogene with a second gene giving rise to a chimeric protein and the subsequent loss of proper regulatory controls and overproduction of Tyr kinase (bcr/abl), is directly assoc’d with the induction of what cancer?
CML
Another example of a proto-onc related disease is APL, which is char’d by a translo betw which two chrom’s, involving what two genes? This translo splits the FISH probe recognition site, so what colors should be observed assuming there’s a translo?
15:17 translo breaking the PML gene of chrom 15 and RARA gene on chrom 17. 2 yellow fusion signal along with 1 red and 1 green.
Describe the two subgroups of tumor suppressors
Gate keepers suppress tumors by regulating the cell cycle or growth inhibition. Caretakers repair DNA dmg and maintain genomic integrity.
Mutations of tumor suppressors are often expressed as solid tumors and are tissue specific (mutations will only cause disease in one or a few cell types). T or F.
True.
A classic gatekeeper mutation of a gene on chrom 13 that controls progression from G1 to S involves what gene? Tumors affect the retinoblasts of the young child eye.
Rb1
Sporadic retinoblastoma is usually unilateral or bilateral? Inherited? Secondary cancer is usually what kind? Which has the earlier age of onset, somatic or familial mutations in a tumor supp gene?
Usually unilateral. Often bilateral. Osteosarcoma. Familial.
Li Fraumeni is a familial cancer syndrome assoc’d with an inheritance of a mutation of what tumor supp? It causes various diff tumors in one family.
p53.
Caretaker mutations result in an inability to repair DNA defects/mutations that results in what sequelae?
Accum of abn DNA/genes with an increase in genome instability, leading to a probable induction of mutation in multiple diff genes such as proto-onc’s and tumor supp’s leading to nonspecific defects in the DNA repair process.
Fanconi anemia, Bloom syn, Ataxia telangiectasia, XP, Coackayne syn are all examples of what type of syndromes? A diverse group of diseases - all very diff clinical phenotypes and caused by genes of different chromosomes.
Breakage syndromes
What things characterize breakage syndromes?
Recessive inheritance, chromosome instability, defective DNA repair mech’s (dmg then leads to fragmentation & breakage of chrom’s), and susceptibility to cancer.
Three genes accounting for DNA mismatch repair that are linked to HNPCC
MSH2, MSH1, MSH6
What regions of the DNA are particularly sensitive to defects in DNA repair because they are subject to replication error due to slippage?
Microsatellites
T or F:
- Microsatellite testing suggests the presence of a defect in MMR.
- The test is direct, looking at specific mutations in MMR gene itself rather than for the effects of that mutation in loci throughout the genome
True. False - indirect.
De novo chromosomal instability may involve all of the following mechanisms:
Breakage or recomb, chrom rearr (dups or dels, t’s or inv’s, tandem dup of genes, generation of supernumerary chrom’s), gain or loss of whole chrom’s.
Mutations in proto-oncogenes have what primary type of cancer as their target?
Leukemias/lymphomas
Loss of heterozygosity
Apparent homozygosity or hemizygosity in a tissue which demonstrates heterozygosity (for markers known to be heterozygous in unaffected tissues) constitutionally.
FISH has been useful in detecting what types of things?
Translo’s like in APL, amplification, bmt success
What type of study allows us to detm relatedness betw diff diseases, for instance to detm if two diseases that present somewhat differently clinically actually have a common basis? This test is valuable in understanding the course of a disease and in designing tx strategies.
Expression arrays.
Unique subsets of mutations characteristic of diff tumors have been identified and specific “signature” panels were developed via what method?
Sequencing
