Cancer Cytogenetics Lecture Flashcards
Why do we study cytogenetics?
Important for proper diagnosis, prognosis, and therapy for patients with leukemia
n or 23
Haploid
2n or 46
Euploid
multiples of n (23, 46, 69…)
Polyploidy
3n or 69 chromosomes
Triploid
4n or 92 chromosomes
Tetraploidy
Gain or loss of chromosome
Aneuploidy
less than 46 chromosomes
Hypodiploid
More than 46 chromosomes
Hyperdiploid
*
Near haploid
*
Pseudodiploid
*
Derivative chromosome
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 chromosome analysis?
only cells in metaphase (cells with a high mitotic rate)
How are chromosomes identified?
- overall size
- placement of centromere
- banding patterns
P arm-
q arm
p arm petite arm - shorter arm
q arm - longer arm
What chemical is added to dividing cells to arrest them in metaphase
Colcemid (derivative colchicine)
Most common method of chromosome banding
Giemsa Banding
Giemsa Banding stains what areas of the chromosomes?
A-T rich areas
A-T rich regions of the chromosome are also known as what areas (3)
Dark areas
G-Positive
Q-Positve
G-C rich regions of the chromosome are knows as what areas? (3)
Light Areas
G-Negative
Q- Dull
From 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 number starting where?
at the area closes to the centromere and get higher in value towards the telomere
47, XX, +21
Female with Down Syndrome
Structural Abnormalities
8
- Translocation
- Robertsonian Translocation
- Insertion
- Inversion
- Deletion
- Duplication
- Isochomosome
- Marker chromosome
Chromosome with a translocation
Derivative Chromosome
Occurs only on acrocentric chromosomes; results the fusion of two chromosomes
Robertsonian Translocation
Relatively rare because 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 involve the centromere
Pericentric Inversions
Inversions that do not include the centromere
Paracentric Inversions
Division of chromosomes is perpendicular to their long axis instead of parallel
Isochomosome
Results from the breakage and rejoining of the end of a chromosome (usually results in partial monosomy)
Ring Chromosome
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 with Maturation
t(15;17)(q24;q21.1) PML/RARA
Acute Promyelocytic Leukemia (APL or PML)
inv(16)(p13q22)
AML with 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 kinase
“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
**Three ways that that chromosomes are identified by cytogenetists?
?
Hyperdiploidy provides favorable prognosis for ALL in ______ but a poor prognosis in _____.
favorable = children poor = adults
