Cytogenetics - Dr. Swisshelm L1 Flashcards
In FISH, __________ are used to identify particular chromosomal regions or rearrangements (translocations) or to diagnose presence of an abnormal chromosome number.
DNA probes specific for individual chromosomes, chromosomal regions or genes
FISH stands for…
Fluorescence in situ hybridization
What phase of cell division must a cell be in for FISH to be utilized?
metaphase or interphase
_________ probes are used to determine the number of copies of a particular chromosome.
Alpha-satellite family
By utilizing probes with different ____________ allows detection of multiple probes simultaneously.
fluorochromes
Array-based comparative genome hybridization can asses relative copy number of DNA sequences but cannot detect _______.
translocations or rearrangements
What is a copy number polymorphism?
a.k.a. CNV = structural variation in DNA
Variation in the number of copies of larger segments of the genome
segments range from 200 bp to 2Mb
can be pathogenic or part of normal human variation
What technology is able to detect CNP’s?
Array comparative genome hybridization (CGH)
A common finding in childhood B-cell acute lymphoblastic leukemia (ALL) with a good prognosis is _________ revealed by ________.
high hyper-diploidy
chromosome and FISH analyses
t(9;22) is diagnostic for what?
Chronic Myelogenous Leukemia (CML)
Treatment for CML is ________.
Tyrosine kinase inhibitors (Gleevec)
PML is treated with
retinoic acid
t(15;17) is diagnostic for ______.
a specific Acute Promyeloid Leukemia (PML)
PML/RARa translocation
What is the centromere (cen) FISH probe used for?
Enumeration - Leukemias
ex: Cen 4, 8, 10, 17, 21
ALL panel, prenatal dx
What is the Locus Specific (LIS) FISH probe used for?
Deletion - leukemias
ex: p53
What is the Fusion (F) or Dual Fusion (DF) FISH probe used for?
Translocations - leukemias
ex: BCR-ABL
PML-RARalpha
Low, hypodiploidy versus
High hyperdiploidy (specifically trisomy 4, 10 or 17)
in pediatric cases of B-cell ALL
What is the prognosis for each?
Low, hypodiploidy = Poor prognosis
loss of tumor supressor genes
High, hyperdiploidy = Good prognosis
The fusion of which two chromosomes / genes cause CML?
Chronic Myelogenous Leukemia is caused by fusion of chromosomes 9 and 22 as follows:
BCR-ABL t(9;22)(q34;q11.2)
How long is a FISH probe usually?
200 bp
What is the Break Apart (BAP) FISH probe used for?
Translocation, rearrangement
ex: MLL (cancer)
What is the Whole Chromosome Paint (WCP) FISH probe used for?
Identifying markers, translocations
ex: WCP 1-22, X, Y
(all studies)
What does BCR in the BCR-ABL fusion stand for?
Breakpoint Cluster Region
is a region of DNA that has a lot of points where the DNA breaks
Why is it possible to have multiple trisomies in the following genotype:
55, XX, +X, +4, +6, +10, +14, +17, +18, +21[9] / 46, XX[10]
What is the prognosis and why?
This is a case of mosaicism. Extra copies of chromosomes X, 4, 6, etc. are seen in some but not all cells. The other (non-cancer) cells have genotype 46, XX[10] meaning that chromosome 10 is fused with chromosome X
Since hyperdiploidy ALL >50, prognosis is good.
What is the distinctive histological finding in cells of APL?
Auer rods
a protein precipitate unique to APL cells
(Acute Promyelocytic leukemia a.k.a. PML)
(Swisshelm Slide)
AML stands for…
Acute Myeloid Leukemia
seen more commonly in adults (but children / young adults also)
4% of all leukemias
What does fusion of PML and RARalpha do to trxn?
When fused they act as repressors and block cell differentiation.
Treatment with retinoic acid switches the complex to coactivators and allows for cell differentiation
What are some of the advantages of CMA?
-detect chromosomal gains and losses
-detect hot-spot abnormalities (ex: 22q11.2 DiGeorge syndrome; subtelomeres)
-detect genome-wide abnormalities; the backbone of the genome
-helps to characterize abnormalities detected by karyotyping
ex; the specific size of an imbalance & the genes involved
A common finding in childhood B-cell leukemia with poor prognosis is _______________ revealed by __________.
low hypodiploidy
FISH and chromosomal analysis
Leukemia can arise in any of the ___________ cells in the __________ pathway. It is usually a mutation that blocks __________ of cells.
progenitor
hematopoetic
differentiation
t(8,21) is diagnostic for…
AML M1/M2
fusion of the ETO gene on 8q22 and AML1 gene on 21q22
no biologic therapy available
chemotherapy
