Cancer Cytogenetics - GO THROUGH END AGAIN

Question 1

which techniques are used for both constitutional and cancer cytogenetics?

Answer 1

• karyotype
• FISH
• chromosome microarray analysis (CMA)

Question 2

CMA compared to karyotyping and fish

Answer 2

• used less frequently to analyze cancer specimens

Question 3

numerical abnormalities

Answer 3

• chromosomal abnormalities that change the number of chromosomes

Question 4

structural abnormalities

Answer 4

• chromosomal abnormalities that change the structure of the chromosome

Question 5

chromosome abnormalities cause disease by

Answer 5

• altering concentration of particular gene products

- altering gene product

Question 6

ways to alter concentration of particular gene products

Answer 6

• duplication or amplification

- deletion or gene interruption

Question 7

what kind of genes are typically duplicated or amplified in cancer

Answer 7

• oncogenes

Question 8

what kind of genes are typically deleted or disrupted in cancer?

Answer 8

• tumor suppressor genes

Question 9

how does cancer alter the gene product?

Answer 9

• produces a few fusion gene with altered expression

- new fusion protein with altered function

Question 10

CML accounts for what percent of leukemia

Answer 10

15-20%

Question 11

CML occurs most frequently in what age group

Answer 11

40-50

Question 12

importance of CML

Answer 12

• first cancer to be associated with a specific recurrent chromosome abnormality

Question 13

chromosome problems in CML

Answer 13

• Ph chromosome secondary to a (9;22) translocation

Question 14

the Philadelphia chromosome contains a

Answer 14

• fusion gene composed of BCR serine/threonine on 22 and ABL1 tyrosine kinase on 9

Question 15

the new fusion BCR/ABL1 tyrosine kinase produced by the fusion gene

Answer 15

• permanently turned-on

- activates a number of signaling pathways

Question 16

permanent activation of BCR/ABL1 fusion kinase leads to

Answer 16

• malignant transformation

- by interfering with basic cellular processes

Question 17

what process is used to identify that BCR/ABL1 fusion gene

Answer 17

• FISH

Question 18

what do you see on FISH in BCR/ABL1 fusion

Answer 18

• yellow fusion signal on part of 9 and part of 22

Question 19

BCR/ABL1 fusion tyrosine kinase as a target for what kind of drug therapy

Answer 19

• tyrosine kinase inhibitors

Question 20

Imatinib (Gleevec) MOA

Answer 20

• tyrosine kinase inhibitor
• blocks ATP binding center of BCR/ABL1 kinase which blocks phosphorylation of various proteins that contribute to cell signaling and uncontrolled growth

Question 21

results of imatinib

Answer 21

• induces long lasting remissions and is well tolerated

Question 22

complete cytogenetic response rate for newly diagnosed CML patients in chronic phase

Answer 22

• 70-98%

Question 23

estimated 3 year survival rate for newly diagnosed CML in chronic phase

Answer 23

• 94%

Question 24

what do we do for patients with early blast phase with first line TKI

Answer 24

• bone marrow/stem cell transplantation

- only cure for CML

Question 25

chromosome abnormalities involved MLL has been implicated in what percent of acute leukemias

Answer 25

- 10% of AML and ALL

Question 26

chromosome abnormalities in acute leukemia located where

Answer 26

- 11q23.3 | - KMT2A gene

Question 27

11q23.3 encodes

Answer 27

- transcriptional regulatory factor essential for embryonic body plan formation and self-renewal of hematopoietic stem cells and immature progenitors

Question 28

what is the prognosis for 11q.23.3 abnormalities

Answer 28

- generally associated with poor prognosis

Question 29

therapies for patients with MLL rearrangements

Answer 29

- no targeted therapies

Question 30

recurrent MLL translocations associated with how many partner genes

Answer 30

- 80

Question 31

mechanism whereby the multiple MLL fusion partners initiate cellular transformation

Answer 31

- largely unknown

Question 32

fusion protein in MLL acts as what kind of mutation

Answer 32

- dominant gain of function

Question 33

what do you see in G-banding karytope of MLL

Answer 33

- short 4 chromosome | - long 11 chromosome

Question 34

what will microarray testing not detect

Answer 34

- balanced rearrangements | - low level mosaicism

Question 35

balanced rearrangements

Answer 35

- no gain or loss present to identify the rearrangements

Question 36

when do we see low level mosaicism/clonal evolution

Answer 36

- minimal residue disease | - data from normal cells masks data from abnormal cells

Question 37

minor clones that provide information about disease progression - in microarray testing

Answer 37

- may be difficult to detect

Question 38

what percentage of abnormalities detected in cells are not detected by CMA?

Answer 38

- abnormalities present in less than 10-15% of cells

Question 39

what are some of the cytogenetic abnormalities missed by traditional cytogenetic testing that microarray can detect

Answer 39

- cryptic rearrangements below level of G-band detection - those without FISH probes - copy number neutral loss of heterozygosity or acquired homozygosity

Question 40

what is a big problem that karyotyping has

Answer 40

- resolution problems

Question 41

what has been identified as a major mechanism of tumor suppressor gene inactivation

Answer 41

- copy number neutral loss of heterozygosity | - acquired homozygosity

Question 42

what technique is required for loss of heterozygosity

Answer 42

- SNP microarray

Question 43

copy number neutral loss of heterozygosity or acquired homozygosity is a common finding in

Answer 43

- all types of leukemia

Question 44

monitoring for cancer is typically done by what cytogenetic techniques

Answer 44

- karyotyping | - FISH

Question 45

what condition has a very specific rearrangement

Answer 45

- CML

Question 46

what condition has a rearrangement that involves multiple partners

Answer 46

- MLL