Chromosome Translocations and Their Role in Blood Cancers

Chromosome Translocations in Leukemia and Lymphomas

Mutation
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Definition: Chromosome Translocations in Cancer

A translocation is a type of abnormal change in the structure of a chromosome that occurs when a part of one chromosome breaks off and sticks to another chromosome. These "mutations" are an important cause of many lymphomas and leukemias.

How Do Chromosome Translocations Occur?

Our chromosomes store all of the genetic information we inherit from our parents.

  We have 23 sets of chromosomes - 1 set from our mothers and 1 set from our fathers - for a total of 46 chromosomes in all.  On each chromosome are hundreds of individual genes that code for everything from the color of our eyes to the proteins that regulate the division of cells in our body.

When our cells divide, a duplicate copy of our chromosomes is made.  Sometimes this process goes wrong, and a portion of a piece of one chromosome may end up attached to another chromosome.

When we talk about genetic changes in cancer it can become very confusing, so we want to make sure one distinction is clear right away. Some genetic changes are inherited and are called germ line mutations, the kind of mutations or other genetic changes you have from birth, but most genetic changes you will hear about are acquired or somatic mutations - mutations and genetic changes that occur in your body after birth and later on in life.

Types of Translocations

There are two types of translocation.

  • Balanced translocations - In a balanced translocation, equal parts of the two chromosomes are exchanged, so there is no extra or missing genetic information.
  • Unbalanced translocations - In an unbalanced translocation, the exchange involves unequal portions of chromosome and leads to extra or missing genes.

    Translocations are indicated using a lower case "t" with the two chromosomes involved in brackets. For example, a translocation between chromosomes 9 and 22 would be indicated by t(9;22).

    Chromosome Translocations and Cancer

    Translocations are a type of damage that may cause a gene to turn into a cancer-causing gene. Scientists do not know what causes these chromosome changes to occur, but we do know of some risk factors for the development of lymphomas and leukemias.  These changes may occur when the DNA in our cells is damaged by a toxin or viral infection, but may occur as a result of a "mistake" in the normal process of cell division. Since our cells divide throughout our lifetimes, the chance that a "mistake" in division will take place increases the older we are.  This is thought to be one of the reasons why many cancers are more common the older we get.  Still, scientists don't have much of an idea what would cause the double strand of DNA to break as it does in translocations.

    To understand how translocations affect cancer risk it can help to understand a little about how genetic changes and mutations result in cancer.

    It's thought that translocations may work by turning oncogenes (cancer-causing genes) on, or by turning tumor suppressor genes to the off position. Tumor suppressor genes code for proteins that repair damaged DNA and essentially act like the brake system in a car, whereas oncogenes act more like an accelerator that is stuck in the on position.

    For the most part, the translocations resulting in leukemias and lymphomas are due to acquired changes in DNA, but this is not always the case. It is usually a combination of genetic changes rather than one or two which results in a cancer, and in some cases, some of these changes may occur before birth.  For example, in some children with acute lymphocytic leukemia, the initial genetic changes may occur while a baby is still present in the womb.

    Translocations in Blood Cancers (Leukemias and Lymphomas)

    Since we've been able to evaluate DNA we are learning that chromosomal translocations play a large role in blood cancers.  It's estimated that translocations are present in up to 90% of lymphomas and over 50% of leukemias.

    Some translocations that are involved in blood cancers include:

    Diagnosing Translocations in Cancer Patients

    Physicians discover chromosome translocation when doing a genetic analysis of biopsy samples. It helps them to identify the disease, plan therapy and predict treatment outcomes.

    Sources:

    American Cancer Society. Do we know what causes non-Hodgkin’s lymphoma? Updated 01/22/16. http://www.cancer.org/cancer/non-hodgkinlymphoma/detailedguide/non-hodgkin-lymphoma-what-causes

    National Cancer Institute. Acute Lymphoblastic Leukemia Treatment – Health Professional Version (PDQ). Updated 12/10/15. http://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq#link/_67_toc

    Nambiar, M., and S. Raghavan. How does DNA break during chromosomal translocations? Nucleic Acid Research. 2011. 39(14):5813-5825.

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