Important Note

Tufts ended funding for its Open Courseware initiative in 2014. We are now planning to retire this site on June 30, 2018. Content will be available for Tufts contributors after that date. If you have any questions about this please write to

Tufts OpenCourseware
Author: Janet M. Cowan, Ph.D.
Color Key
Important key words or phrases.
Important concepts or main ideas.

Clinical Cytogenetics (Part 1)

Acquired Translocations

Occur as part of disease process in the organ affected i.e., bone marrow in leukemia. Not present at birth and the patient's phenotype (appearance) is unchanged by any disease-associated translocation. Cancer associated translocations like t(9;22) are not unique to the individual and are diagnostic for the disease such as chronic myeloid leukemia. Generally result in fusion of genes resulting in an abnormal gene product.

Cytogenetics and Cancer

Mr. E is found to have an abnormally high white cell count on a routine screening at his annual physical. He is referred to a hematologist/oncologist who reviews his blood smear and decides to do a bone marrow aspirate to check. Part of the sample is sent to the lab.

In the Lab

Sample is put into culture, with no PHA, but a growth factor produced by Giant Cell Tumor cells. Sample is incubated overnight, and harvested like a blood. Each cell must be analyzed fully to check that there are 2 x #1, 2 x #2 etc.

In the lab


  • First cancer abnormality described – termed the Philadelphia chromosome
  • Seen in 90-95% of cases of chronic myeloid leukemia (CML)
  • Initially thought to be a deletion, but in 1973 shown to be t(9;22)(q34;q11.2)
  • Can be detected by FISH.
  • Probes span the breakpoints of ABL on 9 (red) and BCR on 22 (green)
  • Exchange of material distal to the breakpoints
  • Brings red signal and green signal together on der(9) and der(22)

Complex Cancer Changes

  • Presence of additional karyotype changes are termed clonal evolution - associated with disease progression
  • Unbalanced translocations (one part of the exchange missing) are common
  • Only affects cells in the bone marrow
  • Patient’s phenotype unchanged

Other Changes Seen in Leukemia

Gain of all or part of a chromosome such as +8, +21

Loss of all or part of a chromosome such as -5, -7, -X, -Y

Inversions such as inv(3), inv(16)

Translocation or exchange of material between two chromosomes - in many cases one or more parts of a translocation may be lost

Karyotype and Prognosis

Change Likelihood of Complete Remission Duration of Remission
inv(3) Low Short
-5/5q- Low Short
-7/7q- Low Short
+8 Variable Variable
t(15;17) High Long
inv(16) High Long

Why do Translocations Recur?

  • Molecular cloning revealed that the breakpoints of recurrent translocations are the location of “oncogenes” - genes involved in driving cell cycle
  • Translocations result in production of abnormal protein that cannot be regulated/overproduction of a normal protein

Why do deletions happen?

  • Deletions result in loss of genes
  • Genes generally involved in control of the cell cycle (“tumor suppressors”)
  • Loss of one copy of gene and possible inactivation of the other copy removes cell cycle control point.

CML and Clonal Evolution

  • As CML enters acute phase, often detect additional karyotype changes.
  • Common changes are: +19 (1%), +Ph1 (15%), +8 (11%), +i(17)(q10) (12%)

FISH and Leukemia

  • Useful for monitoring size of population of cells with previously identified change, such as t(9;22)
  • Also used for patients who have had sex mismatched bone marrow transplant.


  • Normal karyotype = 46 chromosomes: 22 pairs of chromosomes and 2 sex chromosomes (46,XX or 46,XY)
  • Chromosomes divided by the centromere into short (p) and long (q) arms
  • Each chromosome has a number of bands, each of which has been assigned a number
  • Karyotypes written using a system of nomenclature
  • Abbreviations used to describe changes such as t, der, dup, inv
  • Balanced constitutional rearrangements (translocation or inversion) do not alter phenotype and most are unique to a family
  • Unbalanced constitutional rearrangements result in duplication and deletion of material and are associated with changes in phenotype
  • Acquired rearrangements are not unique to a family, but are recurrent
  • Unbalanced rearrangements occur but do not alter the patient’s phenotype
  • Recurrent changes have been correlated with diagnosis and prognosis
  • FISH is a useful technique, used with karyotyping
  • FISH can be used to determine the number of copies of a particular region, detect microdeletions, confirm rearrangements and monitor cell populations in leukemia