What is a translocation?

A translocation is a type of genetic change where a piece of one chromosome breaks off and attaches to a different chromosome. Chromosomes are structures inside your cells that carry DNA, the instructions your body uses to grow, repair itself, and function properly.

When pieces of chromosomes switch places, they can create new combinations of genetic material. Some of these changes have no impact on health, while others can disrupt normal cell behavior. Pathologists often look for translocations when diagnosing cancer or certain blood and bone marrow disorders.

Why do translocations occur?

Translocations occur when DNA within a cell breaks and then repairs itself out of order. This may occur for several reasons:

• Random events: Most translocations occur by chance as cells divide and age.

• Exposure to chemicals: Certain chemicals can damage DNA and increase the chance of incorrect repair.

• Radiation: High levels of radiation can break chromosomes.

• Errors during cell division: Sometimes cells make mistakes when copying or separating their DNA.

Most translocations are not inherited and do not run in families.

What happens to a cell after a translocation?

A translocation can change how specific genes behave. Depending on which genes are affected, several things may happen:

• The cell may grow too quickly: If the translocation activates a gene that encourages growth, the cell may begin dividing faster than it should.

• The cell may lose its growth “brakes”: If a tumor suppressor gene (a gene that normally prevents uncontrolled growth) is disrupted, the cell may lose its ability to control division.

• The cell may continue functioning normally: Some translocations do not affect important genes and have no impact on health.

Whether a translocation is harmful depends on which genes are involved.

How do translocations cause cancer?

Some translocations involve genes that control cell growth, repair, or survival. When these genes are altered, they may send incorrect signals that cause cells to grow and divide uncontrollably. This can lead to cancer.

Translocations may cause cancer in two main ways:

• Turning on an oncogene: Oncogenes are genes that promote cell growth. A translocation can “switch on” an oncogene, telling the cell to grow too fast.

• Turning off a tumor suppressor gene: Tumor suppressor genes act as the cell’s safety system. A translocation can disable this system, allowing uncontrolled growth.

Translocations are commonly found in cancers such as leukemia, lymphoma, sarcoma, and some carcinomas.

Do all translocations cause cancer?

No. Not all translocations lead to cancer. Some are benign (harmless) and do not change how the cell behaves. Others may slightly alter cell function but do not cause disease. Pathologists focus on specific, well-known translocations that drive cancer development because identifying them helps guide diagnosis, prognosis, and treatment.

How do pathologists test for translocations?

Pathologists use specialized laboratory tests to detect translocations. Each test works differently:

• Fluorescence In Situ Hybridization (FISH): Uses glowing (fluorescent) probes that attach to specific chromosomes, allowing rearrangements to be seen under a special microscope.

• Polymerase Chain Reaction (PCR): Makes many copies of targeted DNA segments to detect known translocations quickly and accurately.

• Karyotyping: Examines the complete set of chromosomes under the microscope to find large changes in structure or number.

• Next-Generation Sequencing (NGS): Reads large amounts of DNA at once and can detect both common and rare translocations, even those too small to be seen by other methods.

These tests help pathologists confirm a diagnosis and identify treatments that specifically target the genetic change.

Example of a translocation in a molecular report

Test: Fluorescence In Situ Hybridization (FISH)
Result: Positive for PML::RARA fusion

Interpretation:

A fusion was detected between the PML gene (chromosome 15) and the RARA gene (chromosome 17). This produces an abnormal protein that prevents blood cells from maturing normally, leading to the development of acute promyelocytic leukemia (APL).

Identifying this fusion confirms the diagnosis and suggests the patient is likely to respond well to targeted therapies such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).

This example shows how finding a translocation guides precise diagnosis and highly effective treatment.

What are the most common gene translocations?

Below is a list of well-known translocations and the cancers they are associated with.

Blood and bone marrow cancers

• BCR::ABL1 – Chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL): Creates a protein that drives uncontrolled white blood cell growth.

• CBFB::MYH11 – Acute myeloid leukemia (AML) with inversion 16: Affects genes important for blood cell development.

• PML::RARA – Acute promyelocytic leukemia (APL): Blocks blood cells from maturing; responds well to targeted therapy.

• RUNX1::RUNX1T1 – AML with t(8;21): Changes how early blood cells grow and divide.

• TCF3::PBX1 – ALL with t(1;19): Alters genes that control lymphocyte development.

• ETV6::RUNX1 – Childhood ALL: Common childhood leukemia translocation with a good prognosis.

• MLL::AF4 – Infant ALL: Leads to aggressive leukemia in infants.

• MLL::AF9 – AML with t(9;11): Involves genes that regulate blood cell growth.

• MLL::ELL – AML with t(11;19): Disrupts proteins that control DNA transcription.

Lymphomas

• CCND1::IGH – Mantle cell lymphoma: Turns on a growth-promoting gene called CCND1.

• MYC::IGH – Burkitt lymphoma: Strongly activates MYC, a major driver of cell growth.

• BCL2::IGH – Follicular lymphoma: Helps cancer cells avoid normal cell death.

• BCL6::IGH – Diffuse large B-cell lymphoma (DLBCL): Alters a gene important for B-cell development.

• ALK::NPM1 – Anaplastic large cell lymphoma (ALCL): Activates ALK, a gene that encourages cell growth.

Sarcomas (tumors of bone and soft tissue)

• EWSR1::FLI1 – Ewing sarcoma: Creates an abnormal protein that blocks normal cell maturation.

• SYT::SSX / SS18::SSX1 – Synovial sarcoma: Fuses genes that change how cells grow and divide.

• ETV6::NTRK3 – Congenital fibrosarcoma, secretory breast carcinoma: Activates a growth pathway targeted by NTRK inhibitors.

• FUS::DDIT3 – Myxoid liposarcoma: Affects fat cell development.

• EWSR1::ATF1 – Clear cell sarcoma: Produces a protein that mimics signals from melanoma genes.

• EWSR1::WT1 – Desmoplastic small round cell tumor: Leads to aggressive tumor growth in the abdomen.

• EWSR1::NR4A3 – Myoepithelial carcinoma: Helps identify this rare type of cancer.

Solid tumors (lung, thyroid, prostate, kidney, brain)

• TMPRSS2::ERG – Prostate cancer: Activates ERG, a gene involved in controlling cell behavior.

• ALK::EML4 – Non-small cell lung cancer (NSCLC): Responds well to ALK-targeted therapies.

• NTRK1::TPM3 – Thyroid cancer, soft tissue sarcoma: Activates NTRK1; treatable with NTRK inhibitors.

• RET::CCDC6 – Papillary thyroid carcinoma: Drives abnormal growth in thyroid cells.

• PRCC::TFE3 – Xp11 translocation renal cell carcinoma: Helps confirm this kidney cancer subtype.

• TFE3::NONO – Xp11 translocation renal cell carcinoma: Another fusion seen in young patients with kidney cancer.

• TFEB::PRCC – Renal cell carcinoma: Activates TFEB, a gene involved in cell signaling.

• BRAF::KIAA1549 – Pilocytic astrocytoma: Common in childhood brain tumors; helps confirm diagnosis.

• FGFR3::TACC3 – Glioblastoma, bladder cancer: Activates FGFR3, a gene targeted by several new therapies.

Other tumors

• PLAG1::CTNNB1 – Pleomorphic adenoma of the salivary gland: Helps identify this common benign salivary gland tumor.

• CREB3L1::SS18 – Low-grade fibromyxoid sarcoma: Helps confirm this slow-growing soft tissue tumor.

• EWSR1::PATZ1 – Primary intracranial sarcoma: Seen in rare tumors of the brain.

• NTRK3::ETV6 – Infantile fibrosarcoma: Leads to tumors in infants that often respond to NTRK inhibitors.