Cytogenetics - Dr. Swisshelm L1

Question 0

In FISH, __________ are used to identify particular chromosomal regions or rearrangements (translocations) or to diagnose presence of an abnormal chromosome number.

Answer 0

DNA probes specific for individual chromosomes, chromosomal regions or genes

Question 1

FISH stands for…

Answer 1

Fluorescence in situ hybridization

Question 2

What phase of cell division must a cell be in for FISH to be utilized?

Answer 2

metaphase or interphase

Question 3

_________ probes are used to determine the number of copies of a particular chromosome.

Answer 3

Alpha-satellite family

Question 4

By utilizing probes with different ____________ allows detection of multiple probes simultaneously.

Answer 4

fluorochromes

Question 5

Array-based comparative genome hybridization can asses relative copy number of DNA sequences but cannot detect _______.

Answer 5

translocations or rearrangements

Question 6

What is a copy number polymorphism?

Answer 6

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

Question 7

What technology is able to detect CNP’s?

Answer 7

Array comparative genome hybridization (CGH)

Question 8

A common finding in childhood B-cell acute lymphoblastic leukemia (ALL) with a good prognosis is _________ revealed by ________.

Answer 8

high hyper-diploidy

chromosome and FISH analyses

Question 9

t(9;22) is diagnostic for what?

Answer 9

Chronic Myelogenous Leukemia (CML)

Question 10

Treatment for CML is ________.

Answer 10

Tyrosine kinase inhibitors (Gleevec)

Question 11

PML is treated with

Answer 11

retinoic acid

Question 12

t(15;17) is diagnostic for ______.

Answer 12

a specific Acute Promyeloid Leukemia (PML)

PML/RARa translocation

Question 13

What is the centromere (cen) FISH probe used for?

Answer 13

Enumeration - Leukemias
ex: Cen 4, 8, 10, 17, 21
ALL panel, prenatal dx

Question 14

What is the Locus Specific (LIS) FISH probe used for?

Answer 14

Deletion - leukemias

ex: p53

Question 15

What is the Fusion (F) or Dual Fusion (DF) FISH probe used for?

Answer 15

Translocations - leukemias
ex: BCR-ABL
PML-RARalpha

Question 16

Low, hypodiploidy versus
High hyperdiploidy (specifically trisomy 4, 10 or 17)
in pediatric cases of B-cell ALL
What is the prognosis for each?

Answer 16

Low, hypodiploidy = Poor prognosis
loss of tumor supressor genes

High, hyperdiploidy = Good prognosis

Question 17

The fusion of which two chromosomes / genes cause CML?

Answer 17

Chronic Myelogenous Leukemia is caused by fusion of chromosomes 9 and 22 as follows:

BCR-ABL t(9;22)(q34;q11.2)

Question 18

How long is a FISH probe usually?

Answer 18

200 bp

Question 19

What is the Break Apart (BAP) FISH probe used for?

Answer 19

Translocation, rearrangement

ex: MLL (cancer)

Question 20

What is the Whole Chromosome Paint (WCP) FISH probe used for?

Answer 20

Identifying markers, translocations
ex: WCP 1-22, X, Y
(all studies)

Question 21

What does BCR in the BCR-ABL fusion stand for?

Answer 21

Breakpoint Cluster Region

is a region of DNA that has a lot of points where the DNA breaks

Question 22

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?

Answer 22

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.

Question 23

What is the distinctive histological finding in cells of APL?

Answer 23

Auer rods

a protein precipitate unique to APL cells

(Acute Promyelocytic leukemia a.k.a. PML)
(Swisshelm Slide)

Question 24

AML stands for…

Answer 24

Acute Myeloid Leukemia
seen more commonly in adults (but children / young adults also)
4% of all leukemias

Question 25

What does fusion of PML and RARalpha do to trxn?

Answer 25

When fused they act as repressors and block cell differentiation.

Treatment with retinoic acid switches the complex to coactivators and allows for cell differentiation

Question 26

What are some of the advantages of CMA?

Answer 26

-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

Question 28

A common finding in childhood B-cell leukemia with poor prognosis is _______________ revealed by __________.

Answer 28

low hypodiploidy

FISH and chromosomal analysis

Question 29

Leukemia can arise in any of the ___________ cells in the __________ pathway. It is usually a mutation that blocks __________ of cells.

Answer 29

progenitor
hematopoetic
differentiation

Question 30

t(8,21) is diagnostic for…

Answer 30

AML M1/M2
fusion of the ETO gene on 8q22 and AML1 gene on 21q22
no biologic therapy available
chemotherapy