Cancer Cytogenetics - Intro, Methods, Nomenclature

Question 1

Name 4 example uses for cytogenetics in cancer diagnostics & treatment.

Answer 1

1. Making diagnosis and classifications
2. Risk stratification / prognostication
3. Identifying targetable therapies
4. Monitoring effects of therapy or disease progression

Question 2

Describe “Class I” and “Class II” mutations in hematologic malignancies.

Answer 2

Class I: Gives proliferative or survival advantage

Class II: Blocks differentation

Question 3

Define: Clone

Answer 3

A cell population derived from a single progenitor.

Question 4

Define: Recurring abnormality

Answer 4

A numerical or structural abnormality noted in multiple patients who have a similar disease.

Question 5

Define: Modal number

Answer 5

The most common chromosome number in a tumor population.

Question 6

In what number of cells must the following abnormalities be seen to be called?

• Structural rearrangement
• Chromosomal gain
• Chromosomal loss

Answer 6

Rearrangement - Two cells
Chromosomal gain - Two cells
Chromosomal loss - Three cells (can lose chromosomes when dropping)

Question 7

Define:

• cen
• i
• mar
• der
• add

Answer 7

cen - centromere
i - isochromosome
mar - marker chromosome
der - derivative chromosome
add - additional material

Question 8

What is an isochromosome?

Answer 8

A chromosome with two copies of one arm due to loss and duplication.

Question 9

What is a marker chromosome?

Answer 9

A chromosome that cannot be identified in karyotyping.

Question 10

What is a derivative chromosome?

Answer 10

Basically, a very rearranged chromosome.

Question 11

What is the difference between “-“ and “del”?

Answer 11

“del” refers to a terminal or interstitial deletion, while “-“ can refer to a deletion or whole chromosome loss. “-“ should not be used in karyotypes to describe deletions.

Question 12

Explain the region described by this nomenclature: 4q21.2

Answer 12

Chromosome 4
Long arm
Region 2
Band 1
Sub-band 2

Question 13

In what ways is cancer cytogenetic analysis different than constitutional?

Answer 13

1. Culturing does not require mitogens and is done for a shorter period (cancer cells naturally proliferative)
2. Cell populations are heterogeneous
3. Chromosome morphology is worse.

Question 14

What are some appropriate indications for cancer cytogenetics?

Answer 14

1. All leukemias & lymphomas, including evolving, relapsed, and residuals.
2. Follow-up samples at RD or CR (if diagnostic sample was abnormla)
3. Opposite-sex post-transplant samples.

Question 15

What tissues can be used for cancer cytogenetics?

Answer 15

Bone marrow biopsies & aspirates

Lymph node and tumor mass biopsies

Peripheral blood

Effusions or CSF

Question 16

BRIEFLY review the processing of tissue for cancer cytogenetics.

Answer 16

1. Short term culture
2. Harvest with colcemid arrest, hypotonic lysis, and 3:1 fixation.
3. Slide making by dropping, heating, and treatment with trypsin.
4. Banding or FISH.

Question 17

What does G-banding highlight?

Answer 17

Dark bands: AT-rich and gene-poor regions

Light bands: GC-rich and gene-rich regions.

Question 18

What are some advantages and weaknesses of FISH over karyotyping?

Answer 18

Pros: Doesn’t require metaphases, higher sensitivity, faster/simpler and less subjective.

Cons: Targeted, limited number of probes.

Question 19

Describe 3 FISH probe designs.

Answer 19

Counting signals (centromere probes)

Dual-fusion probes (detects translocations)

Break-apart probes

Question 20

What are the strengths and weaknesses of SNP microarray analysis?

Answer 20

Pros: High-resolution, cost effective, and objective.

Cons: Does not detect balanced translocations or low-level mosaicism.

Question 21

How does SNP microarray work?

Answer 21

By detection of SNP alleles to detect losses of heterozygosity, indicating chromosomal losses or gains.