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MYC, BCL2 and BCL6 testing: what the result means | CION Cancer Clinics
A FISH test checks whether the MYC, BCL2 and BCL6 genes have broken and moved inside lymphoma cells. If MYC and BCL2 have both moved, the lymphoma is called double hit, and your haematologist may recommend a different or more intensive plan. It is done on your existing biopsy block. This page explains what each result means and what it cannot tell you. At CION Cancer Clinics, our haematology team plans myeloma and lymphoma care with you, discussed at a tumour board and explained in plain words.
On this page
- Why is MYC, BCL2 and BCL6 testing done in lymphoma?
- What does each of the three genes do?
- How is a FISH test actually done?
- Is double expressor the same as double hit?
- What do the words on a FISH report mean?
- What happens if the result comes back positive?
- What do families often misread about this test?
- Common questions about MYC, BCL2 and BCL6 testing
The short answer
Why is MYC, BCL2 and BCL6 testing done in lymphoma?
This test checks whether three genes, MYC, BCL2 and BCL6, have broken and moved in the lymphoma cells. When MYC has moved together with BCL2, the lymphoma is called "double hit". That changes its name and can change the treatment your haematologist recommends.
What the test looks at
Genes sit on chromosomes, the long strands of DNA inside every cell. Sometimes a piece of a chromosome breaks off and joins another. When that break lands next to a growth gene, the gene can get stuck in the "on" position. The test looks for these breaks, which the report calls a rearrangement or translocation.
Who is usually tested
It is most often done in diffuse large B-cell lymphoma (DLBCL) and in lymphomas that look very fast-growing under the microscope. Some centres test everyone with DLBCL. Others test when the stains, the cell appearance or the subtype suggest a higher chance of a gene change.
Who it rarely changes things for
If a gentle, low-intensity plan has already been chosen because of age or other illnesses, a positive result may not alter that plan. It can still be worth knowing, but ask your team how they would use it before paying for it.
This test is done on the same biopsy block. It usually does not need a new biopsy.The three genes
What does each of the three genes do?
Each one is a normal gene that every B cell has. The problem is when a break leaves it switched on.
MYC
A gene that tells the cell to grow and divide. Stuck in the "on" position, it drives very fast growth. A MYC break on its own is found in some DLBCL, and it matters most when paired with another break.
BCL2
A gene that stops the cell from dying when it should. Stuck "on", it lets damaged cells survive. A MYC break together with a BCL2 break is the combination that defines a double hit lymphoma.
BCL6
A gene that keeps B cells in their early, growing stage. Its breaks are fairly common. How much a MYC plus BCL6 combination matters is still debated, and the latest classifications treat it differently.
What that means for you
- Ask how your lab labels this result
- Ask whether it changed the plan
Not sure whether this applies to you?
Ask an oncologistIn the laboratory
How is a FISH test actually done?
The block is retrieved
The lab takes the wax block from your original biopsy. Thin slices are cut and placed on glass slides.
Glowing probes are added
FISH stands for fluorescence in situ hybridisation. Small pieces of DNA tagged with coloured light-emitting dyes attach to each gene being checked.
Cells are counted
Under a special microscope, a normal gene shows its colours together. A broken gene shows them split apart. The scientist counts many cells before calling a result.
The report is issued
Each gene is reported as rearranged or not rearranged. If the sample is too small or poorly preserved, the report may say the result could not be given.
Two terms often confused
Is double expressor the same as double hit?
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On your report
What do the words on a FISH report mean?
- Rearrangement or translocation
- The gene has broken and joined another part of the DNA. This is the finding that counts.
- Break-apart probe
- The type of probe that shows a split signal when a gene has broken. The report may name it.
- Amplification or extra copies
- More copies of the gene than normal. This is different from a rearrangement and does not make a lymphoma double hit.
- HGBL with MYC and BCL2 rearrangements
- The formal name for a double hit lymphoma. HGBL means high-grade B-cell lymphoma.
- Triple hit
- MYC, BCL2 and BCL6 have all broken. It is handled much like a double hit.
What it means for the plan
What happens if the result comes back positive?
A double hit result usually leads your haematologist to review the treatment plan. There is no single agreed treatment for it. Some teams choose a more intensive combination such as DA-EPOCH-R. Others stay with R-CHOP, particularly when the disease is limited or when a stronger plan would not be safe.
Other things the team may add
Double hit lymphoma has a higher chance of spreading to the brain and spinal cord. So your team may check the spinal fluid and discuss treatment to lower that risk. A clinical trial may also be worth asking about, because the evidence for any one approach is still limited.
Who a stronger plan may not suit
Intensive chemotherapy needs more hospital stays and carries more infection risk. It may not suit people who are older, have heart or kidney problems, or are very unwell at diagnosis. A careful plan that you can finish safely is often more useful than a stronger one that must be stopped.
What this page cannot tell you
It cannot tell you your outlook. That depends on the whole case, including stage, the IPI score and response to treatment. A negative result is also not a promise of an easy course. Ask your haematologist what the result means for you.
Commonly believed
What do families often misread about this test?
They sound alike but are different findings. Double expressor comes from protein stains and is fairly common. Double hit comes from a gene test and is much rarer. Only a FISH result can confirm a double hit.
These breaks happen only inside the lymphoma cells during a person's life. They are not passed down in families. Relatives do not need testing for them.
If you are very unwell, your team may start treatment or steroids while the result is awaited, and adjust later. Waiting too long can let a fast lymphoma grow. Ask what the plan is while results are pending.
It is a harder lymphoma to treat, but people do respond to treatment, and some stay in remission, meaning no sign of lymphoma on tests. It changes the plan. It does not end the options.
Questions we are asked
Common questions about MYC, BCL2 and BCL6 testing
How long does the FISH result take?
Usually longer than the first biopsy report, because it needs separate lab work and is sometimes sent to a specialist lab. Ask the lab or your team for their usual timeline. If you are unwell while waiting, tell your haematologist, because treatment may be started first and adjusted later.
Can FISH be done on a small needle biopsy?
Sometimes, but small samples may not contain enough cells for a clear answer. This is one reason haematologists prefer a larger surgical or core biopsy of a lymph node at diagnosis. If your result says the test failed, ask whether a repeat biopsy is needed or whether it would change the plan.
Only MYC is rearranged. Is that a double hit?
No. A MYC break on its own is called a single hit. It may still be taken into account when your team plans treatment, but the lymphoma is usually still classed as DLBCL. Ask your haematologist whether it changes anything in your case.
Is the FISH test available in Hyderabad?
Yes, several pathology laboratories in Hyderabad and other large Indian cities offer lymphoma FISH panels. Your block can usually be sent from wherever the biopsy was read. CION's haematology team can guide you on where the test is done and what to ask for.
Does insurance or Aarogyasri pay for this test?
It depends on the scheme and the package your treatment falls under. Some cancer packages include diagnostic tests and some do not. Aarogyasri, PM-JAY, CGHS, ECHS, EHS and cashless insurers each have their own rules, and these change. Check your current cover before the test is arranged.
Should the test be repeated if the lymphoma comes back?
A new biopsy is often taken at relapse to confirm the diagnosis. FISH may be repeated on that sample if it was not done before, or if the lymphoma looks different. Your haematologist will decide whether the result would change the choice of next treatment.
Does a double hit result mean I need a transplant?
Not automatically. Transplant in first remission is not routine for double hit lymphoma in most current practice. It is usually discussed if the lymphoma does not respond or comes back. CION does not perform transplants itself, and coordinates referrals with qualified centres when needed.
What should I ask my haematologist about this result?
Ask which genes were tested, whether each was rearranged, and what the formal diagnosis now is. Ask whether the result changed the treatment plan, whether brain and spine checks are needed, and whether a clinical trial is open. Keep a copy of the full FISH report with your records.
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Sources
- National Cancer Institute — Adult Non-Hodgkin Lymphoma Treatment (PDQ) - Health Professional Version
- Leukemia & Lymphoma Society — Non-Hodgkin Lymphoma
- American Cancer Society — Non-Hodgkin Lymphoma
- National Cancer Institute — Definition of fluorescence in situ hybridization
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.
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