cytogenetics Flashcards
what cytogenetic tools are used for diagnosing cancer
Fluorescent in situ hybridization (FISH), chromosome microarray analysis, and karyotyping (G-banding)
what cytogenetic tools are used for monitoring cancer
Fluorescent in situ hybridization (FISH) and karyotyping (G-banding)
advantages of chromosome microarray analysis
- picks up small fragments that show up as low resolution on karyotypes
- picks up copy number neutral loss of heterozygosity or acquired homozygosity
disadvantages of chromosome microarray analysis
- 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%)
FISH strategy used depends on/varies due to
whether you are testing for a single specific rearrangement or a rearrangement that involved multiple partners
what type of FISH would you use for rearrangement that involved multiple partners
break apart FISH
chronic myeloid leukemia involves what translocation of what genes
9 - BCR 22 - ABL
BCR/ABL moves to chromosome
22
BCR/ABL leads to
formation of tyrosine kinase that activates CML proliferation pathway
which medication is used to target BCR/ABL fusion gene
imatinib (gleevec)
95% of patients with CML have
BCR/ABL fusion
1st, 2nd, and 3rd line treatment for CML?
1st: imatinib (gleevec) 2nd: another medication 3rd: bone marrow transplant
why is it important to monitor CML with G-banding as well as FISH
G-banding can pick up with there is progression of CML outside of the 9 22 translocation that FISH is monitoring
imatinib mechanism
binds BCR/ABL to prevent ATP from binding and phosphorylating tyrosine kinase stops signaling pathway
chromosome abnormalities that are acquired
leukemias that result in numerical structural abnormalities
how do chromosome abnormalities cause disease
- altering concentration of gene products 2. altering product leading to new fusion gene
CML accounts for ______ leukemia and occurs most frequently in _______ years olf
15-20% and 40-50
what was the first cancer to be associated with a specific recurrent chromosome abnormality?
CML
when was Ph first reported
1960
when was it discovered that Ph is secondary to chromosome 9;22 translocation
1973
what is Ph
Ph= 9;22 translocation that produces dual fusion gene with BCR/ABL mutation
tyrosine kinase produced by BCR/ABL is
permanently turned on and activates a number of signal pathways that leads to malignant transformations
imatinib works well because
induces long lasting remissions and is tolerated well
what is the gene mutation associated with acute leukemia
MLL (KMT2A) gene
why is acute leukemia different than CML in regard to cytogenetic testing?
- 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
mechanism of MLL (KMT2A)
largely unknown but does act as a gain or function mutation
a transcriptional regulatory factor for acute leukemia is
11q23.3
break apart probe allows us to detect MLL rearrangements but not
partner chromosome locus
layout of AA, AB, and BB SNP data
AA AB BB
