cytogenetics

Question 1

what cytogenetic tools are used for diagnosing cancer

Answer 1

Fluorescent in situ hybridization (FISH), chromosome microarray analysis, and karyotyping (G-banding)

Question 2

what cytogenetic tools are used for monitoring cancer

Answer 2

Fluorescent in situ hybridization (FISH) and karyotyping (G-banding)

Question 3

advantages of chromosome microarray analysis

Answer 3

• picks up small fragments that show up as low resolution on karyotypes
• picks up copy number neutral loss of heterozygosity or acquired homozygosity

Question 4

disadvantages of chromosome microarray analysis

Answer 4

• does not pick up balanced rearrangement (does not pick up equal amounts of gain and loss of function)
• does not pick up low levels of mosaicism/clonal evolution (minimal residual disease, minor clones, and does not pick up abnormalities that are less than 10-15%)

Question 5

FISH strategy used depends on/varies due to

Answer 5

whether you are testing for a single specific rearrangement or a rearrangement that involved multiple partners

Question 6

what type of FISH would you use for rearrangement that involved multiple partners

Answer 6

break apart FISH

Question 7

chronic myeloid leukemia involves what translocation of what genes

Answer 7

9 - BCR 22 - ABL

Question 8

BCR/ABL moves to chromosome

Answer 8

22

Question 9

BCR/ABL leads to

Answer 9

formation of tyrosine kinase that activates CML proliferation pathway

Question 10

which medication is used to target BCR/ABL fusion gene

Answer 10

imatinib (gleevec)

Question 11

95% of patients with CML have

Answer 11

BCR/ABL fusion

Question 12

1st, 2nd, and 3rd line treatment for CML?

Answer 12

1st: imatinib (gleevec) 2nd: another medication 3rd: bone marrow transplant

Question 13

why is it important to monitor CML with G-banding as well as FISH

Answer 13

G-banding can pick up with there is progression of CML outside of the 9 22 translocation that FISH is monitoring

Question 14

imatinib mechanism

Answer 14

binds BCR/ABL to prevent ATP from binding and phosphorylating tyrosine kinase stops signaling pathway

Question 15

chromosome abnormalities that are acquired

Answer 15

leukemias that result in numerical structural abnormalities

Question 16

how do chromosome abnormalities cause disease

Answer 16

1. altering concentration of gene products 2. altering product leading to new fusion gene

Question 17

CML accounts for ______ leukemia and occurs most frequently in _______ years olf

Answer 17

15-20% and 40-50

Question 18

what was the first cancer to be associated with a specific recurrent chromosome abnormality?

Answer 18

CML

Question 19

when was Ph first reported

Answer 19

1960

Question 20

when was it discovered that Ph is secondary to chromosome 9;22 translocation

Answer 20

1973

Question 21

what is Ph

Answer 21

Ph= 9;22 translocation that produces dual fusion gene with BCR/ABL mutation

Question 22

tyrosine kinase produced by BCR/ABL is

Answer 22

permanently turned on and activates a number of signal pathways that leads to malignant transformations

Question 23

imatinib works well because

Answer 23

induces long lasting remissions and is tolerated well

Question 24

what is the gene mutation associated with acute leukemia

Answer 24

MLL (KMT2A) gene

Question 25

why is acute leukemia different than CML in regard to cytogenetic testing?

Answer 25

1. decreased prognosis (only 10% of acute leukemias involve MLL) 2. no targeted therapies 3. requires break apart FISH 4. translocations associated with at least 80 partner genes

Question 26

mechanism of MLL (KMT2A)

Answer 26

largely unknown but does act as a gain or function mutation

Question 27

a transcriptional regulatory factor for acute leukemia is

Answer 27

11q23.3

Question 28

break apart probe allows us to detect MLL rearrangements but not

Answer 28

partner chromosome locus

Question 29

layout of AA, AB, and BB SNP data

Answer 29

AA AB BB