Translocation: Definition


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A translocation is a genetic change in which a piece of one chromosome breaks off and joins a different chromosome. Chromosomes are the structures in a cell that carry DNA. Some translocations cause cancer. Others cause no harm.

Pathologists test for translocations to diagnose many blood cancers, lymphomas, and sarcomas. This article explains what a translocation is, how it can cause cancer, how pathologists test for it, and what your report may say.

What is a translocation?

A translocation happens when two chromosomes break and swap pieces. Each chromosome carries many genes. When the pieces rejoin in the wrong place, genes can end up next to new neighbors. This can change how those genes work.

Doctors write a translocation as “t” followed by the two chromosome numbers. For example, t(9;22) means a swap between chromosome 9 and chromosome 22. This translocation creates the Philadelphia chromosome, a shortened chromosome 22.

Understanding Chromosome Translocation

How is a translocation different from a fusion or a rearrangement?

These three terms overlap, but they mean different things:

  • Rearrangement. A rearrangement is any change in the structure of a chromosome. Translocations are one type.
  • Translocation. A translocation is a rearrangement between two different chromosomes.
  • Fusion. A fusion is a new gene made when two genes join. A translocation often creates a fusion, but not always.

Some fusions come from other kinds of rearrangement. In lung cancer, the EML4::ALK fusion forms when part of chromosome 2 flips around. It does not involve a second chromosome. Some translocations also work without a fusion. In follicular lymphoma, t(14;18) moves the BCL2 gene next to a strong growth switch.

How are fusion genes written on a report?

Reports write a fusion as two gene names joined by a double colon. The gene at the start of the new gene comes first. For example, BCR::ABL1 means the start of the BCR gene has joined the end of the ABL1 gene. An international gene naming committee recommended this style in 2021. Older reports may use a hyphen or a slash instead, such as BCR-ABL1.

How can a translocation cause cancer?

A translocation causes cancer when it changes a gene that controls cell growth. It can do this in two main ways:

  • Making an abnormal protein. The fusion gene makes a new protein that keeps telling the cell to grow. In chronic myeloid leukemia, the BCR::ABL1 protein is stuck in the “on” position.
  • Turning on a nearby gene. The translocation moves a gene next to a strong switch. The gene then makes too much of its protein. In follicular lymphoma, extra BCL2 protein keeps abnormal B cells from dying.

Many translocations do not affect important genes and cause no harm. Pathologists focus on translocations that are known to drive specific cancers.

Are translocations inherited?

Most translocations found in cancer are not inherited. They develop in the tumor cells during a person’s life. They are not present in the rest of the body and cannot be passed on to children. Pathologists call these changes acquired, or somatic. See somatic mutation.

A different kind of translocation is present in every cell from birth. About 1 in 625 people carry a balanced translocation, in which no genetic material is lost. These people are usually healthy. They may have a higher risk of miscarriage or of having a child with a disability. A genetics team can explain these risks.

Which cancers have translocations?

Translocations are common in blood cancers, lymphomas, and sarcomas. Each translocation is often linked to a specific cancer type. Examples include:

How do pathologists test for translocations?

Pathologists use several tests to find translocations. Each test answers a slightly different question:

  • Karyotype. A karyotype shows all the chromosomes under a microscope. It finds large changes, such as the Philadelphia chromosome.
  • FISH. Fluorescence in situ hybridization uses glowing probes that stick to specific genes. It can show that a gene has broken, but it may not show which partner it joined.
  • PCR. Polymerase chain reaction finds a known fusion. It is very sensitive, so doctors use it to track BCR::ABL1 levels during treatment.
  • Next-generation sequencing. Next-generation sequencing reads many genes at once. RNA sequencing can name both partners of a fusion.

What might my report say about a translocation?

Your report may describe a translocation in a few standard ways. Each laboratory phrases it a little differently:

  • A translocation by chromosome number. For example, “t(9;22) detected” on a karyotype.
  • A named fusion. For example, “Positive for BCR::ABL1 fusion.” The test found the fusion gene.
  • A gene rearrangement. For example, “EWSR1 rearrangement detected.” FISH found a broken gene but did not name its partner.
  • Not detected. The test did not find the translocation it looked for. Other changes may still be present.

Questions to ask your doctor

  • Which translocation or fusion did the test find?
  • Which test did the laboratory use?
  • Does this result confirm my diagnosis?
  • Does this translocation affect my treatment options?
  • Is there a targeted treatment for this change?
  • Will you use this test to monitor my treatment response?
  • Is this change only in the tumor, or could I have inherited it?
  • Do I need to see a genetics team?

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