Cancer Cytogenetics Flashcards
Why do we study cytogenetics?
Important for diagnosis, prognosis, and therapy for patients w/ leukemia
n = 23 c’somes
Haploid
2n = 46 c’somes
Euploid
Multiples of n (23, 46, 69)
Polyploidy
3n = 69 c’somes
Triploid
4n = 92 c’somes
Tetraploidy
Gain or loss of c’somes
Aneuploidy
Less than 46 c’somes
Hypoploid
More than 46 c’somes
Hyperploid
23-34 c’somes
Near haploid
Cell w/ 46 c’somes and structural abnormalities
Pseudodiploid
C’some w/ a translocation
Derivative c’some (der)
Clonal proliferations of malignant leukocytes that arise initially in the bone marrow before disseminating to the peripheral blood, lymph nodes and other organs
Leukemia
DNA double helix looped around histone proteins
Nucleosome
Twisting of nucleosomes into a chromatin thread
Solenoid
Name the 5 processes of the cell cycle and know what they do
G0: resting/quiescence G1: growth before DNA synthesis S: DNA synthesis G2: growth M: division occurs (PMAT)
What cells are used for collection of specimens for c’some analysis?
Only cells in metaphase re used (chromatin is maximally condensed)
- Cells w/ high mitotic rate ar eusually chosen or cells that can be stimulated to divide (such as PB lymphs)
What three things help cytogenetists identify c’somes?
- Overall size
- Placement of centromere
- Banding patterns
P and Q arms
P arm = petite arm (shorter)
Q arm = longer arm
What chemical is added to dividing cells to arrest them in metaphase?
Colcemid (derivative colchicine)
Most common method of c’some banding
Giemsa banding
Giemsa banding stains what areas of the c’somes?
A-T rich areas (not transcriptional aka late replicating)
G-C rich areas of the c’some are also known as what areas?
Light areas
G-negative
Q-dull
A-T rich areas of the c’some are also known as what areas?
Dark area
G-positive
Q-bright
From the left to right name the karyotype nomenclature
- Modal number of chromosomes in the cell
- Sex chromosome designation
- Chromosomes
- Arm
- Band
- Sub-band
Regions, bands, and sub-bands are numbered staring where?
At the area closest to the centromere and get higher in value towards the telomere
47, XX, +21
Female w/ Down Syndrome
8 structural abnormalities
- Translocation
- Robertsonian Translocation
- Insertion
- Inversion
- Deletion
- Duplication
- Isochomosome
- Marker chromosome
C’some w/ a translocation
Derivative c’somes
Occurs only on acrocentric c’somes; results the fusion of two c’somes
Robertsonian translocation
Relatively rare b/c three separate breaks are required
Insertion
- Interstitial involved two breaks and the loss of a segment between the breaks
- Terminal involve only one break
Deletion
Inversions that involve the centromere
Pericentric inversions
Inversions that don’t include the centromere
Paracentric inversions
Division of c’somes is perpendicular to their long axis instead of parallel
Isochromosome
Results from the breakage and rejoining of the end of a c’some (usually results in partial monosomy)
Ring c’some
What is a molecular cytogenetic test that utilizes fluorescently labeled probes that are hybridized to metaphase or interphase cells
FISH (Flourescence in Situ Hybridization)
You do not need ____ to perform FISH
Dividing cells
____ results from multiple and sequential genetic mutations in a somatic cell. At some juncture, a critical mutation occurs and the cell becomes self-perpetuating (aka clonal)
Cancer
What is a cell population derived from a single progenitor
Clone
How do cytogenetics identify clones
- 2 or more cells contain the same structural abnormality or supernumerary marker chromosomes
- 3 or more cells are missing the same chromosomes
What aberration frequently found as the sole karyotype abnormality associated with a particular tumor? Aka “stem-line”
Primary aberration
Aberration that is rarely found alone and develops in cells already carry a primary aberration
Secondary aberration
t(8;21)(q22;q22.3) RUNX1T1 (ETO)/RUNXX1
AML w/ maturation
t(15;17)(q24;q21.1) PML/RARA
Acute promyelocytic leukemia (APL or PML)
inv(16)(p13q22)
AML w/ abnormal bone marrow eosinophils
t(9;22)(q34;q11.2) CVR/ABL1
know the two names
Chronic Myelogenous Leukemia (CML) and/or Philadelphia Chromosome
t(16;16)(p13;q22)
AML with abnormal bone marrow eosinophils
Who discovered that (9;22) is responsible for CML and that t(8;22) is responsible for AML?
Janet Rowley
What is the drug to treat CML?
Imatinib
The BCR-ABL Gene codes for ______ ______ that is perpetually turned “____”
Tyrosine Kinease; “on”
The BCR-ABL gene leads to rapid progression through the cell cycle and thus rapid and uncontrollable cell ________.
Proliferation
What prevents phosphorylation of the BCR-ABL TK?
Imatinib
SNP allows for much greater resolution than what?
Karyograms and FISH
Hyperdiploidy provides favorable prognosis for ALL in ______ but a poor prognosis in _____.
Favorable = children Poor = adults
