Lectures 15&16: Cancer Genetics

Question 1

Uncontrolled cell growth char’d by a change in the normal organizational pattern of tissues or cells, including karyotypic changes and metastasis.

Answer 1

Malignancy

Question 2

Malignant tumor of potentially unlimited growth that expands locally by invasion and systemically by metastasis.

Answer 2

Cancer

Question 3

Sarcoma is to mesenchymal tissue (bone, cartilage, muscle, fat) as carcinoma is to ??

Answer 3

Epitheloid tissue

Question 4

Leukemia affect WBCs from the bone marrow, while lymphomas affect WBCs from the the ??

Answer 4

Spleen and lymph nodes.

Question 5

Cancer most likely results from a combination of what two effects?

Answer 5

Environmental and cellular effects.

Question 6

List hallmarks of cancer

Answer 6

• 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)

Question 7

Structurally important “housekeeping” genes involved in cell proliferation and development are called? Name some general examples of what they meddle in.

Answer 7

Proto-oncogenes. Examples include growth factors, cell surface receptors, intracellular signal transduction, DNA binding proteins (txn), reg of cell cycle.

Question 8

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?

Answer 8

False. Dominant - requires 1 hit.

Question 9

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?

Answer 9

CML

Question 10

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?

Answer 10

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.

Question 11

Describe the two subgroups of tumor suppressors

Answer 11

Gate keepers suppress tumors by regulating the cell cycle or growth inhibition. Caretakers repair DNA dmg and maintain genomic integrity.

Question 12

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.

Answer 12

True.

Question 13

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.

Answer 13

Rb1

Question 14

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?

Answer 14

Usually unilateral. Often bilateral. Osteosarcoma. Familial.

Question 15

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.

Answer 15

p53.

Question 16

Caretaker mutations result in an inability to repair DNA defects/mutations that results in what sequelae?

Answer 16

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.

Question 17

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.

Answer 17

Breakage syndromes

Question 18

What things characterize breakage syndromes?

Answer 18

Recessive inheritance, chromosome instability, defective DNA repair mech’s (dmg then leads to fragmentation & breakage of chrom’s), and susceptibility to cancer.

Question 19

Three genes accounting for DNA mismatch repair that are linked to HNPCC

Answer 19

MSH2, MSH1, MSH6

Question 20

What regions of the DNA are particularly sensitive to defects in DNA repair because they are subject to replication error due to slippage?

Answer 20

Microsatellites

Question 21

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

Answer 21

True. False - indirect.

Question 22

De novo chromosomal instability may involve all of the following mechanisms:

Answer 22

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.

Question 23

Mutations in proto-oncogenes have what primary type of cancer as their target?

Answer 23

Leukemias/lymphomas

Question 24

Loss of heterozygosity

Answer 24

Apparent homozygosity or hemizygosity in a tissue which demonstrates heterozygosity (for markers known to be heterozygous in unaffected tissues) constitutionally.

Question 25

FISH has been useful in detecting what types of things?

Answer 25

Translo’s like in APL, amplification, bmt success

Question 26

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.

Answer 26

Expression arrays.

Question 27

Unique subsets of mutations characteristic of diff tumors have been identified and specific “signature” panels were developed via what method?

Answer 27

Sequencing