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Large genomic rearrangements: the gene faults a panel can miss | CION Cancer Clinics
Some inherited gene faults are not spelling mistakes. A whole section of the gene is missing, doubled or flipped, and ordinary sequencing can read straight past it. Most modern panels now add a check for this, but older tests often did not. This page explains the kinds of rearrangement, why they are hard to see, and when a family should ask whether theirs was looked for. At CION Cancer Clinics in Hyderabad, our oncologists review your family history with you and guide you to the right genetic counselling and testing.
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Medically reviewed by Dr. Naresh GunduConsultant Medical Oncologist · MBBS, DNB (Internal Medicine), DM (Medical Oncology, AIIMS) · last reviewed September 2026, next review due September 2027
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On this page
- What is a large genomic rearrangement, and why can a panel miss it?
- What shapes can a large rearrangement take?
- Why does ordinary sequencing struggle to see them?
- The words you will meet, in plain language
- A spelling change and a rearrangement, compared
- What this page cannot tell you
- Four things families assume, and what is actually true
- Common questions about large rearrangements
The short answer
What is a large genomic rearrangement, and why can a panel miss it?
A large genomic rearrangement is a gene fault where a whole section of the gene is missing, doubled, flipped or moved. Standard sequencing is built to spot spelling mistakes in a gene, one letter or a few letters at a time. A missing paragraph can slip past it unless the laboratory runs an extra check designed to count how many copies of each section are there.
Why this matters to a family
A rearrangement breaks a gene just as surely as a spelling mistake does, and it carries the same meaning for relatives. If a test could not see it, a family can be told "no fault found" when one is there. That is one reason an older negative result is sometimes worth another look.
How common are they?
They are the minority of inherited faults, and how often they turn up varies by gene and by population. In some genes, such as BRCA1 and the genes behind Lynch syndrome, they make up a meaningful share of the faults families carry. Most modern panels now look for the common types, but not every test does, and not every type is easy to see.
Ask whether your report says "deletion and duplication analysis" was done. If it does not say, ask the laboratory.The four kinds
What shapes can a large rearrangement take?
Think of a gene as a paragraph of instructions made up of several sentences. Each of these changes damages the paragraph in a different way.
Deletion
One or more sentences are missing altogether. The cell reads a shortened paragraph and the instruction no longer makes sense. This is the commonest kind, and most current panels are set up to find it.
Duplication
A section appears twice. It sounds harmless, but an extra copy in the wrong place can scramble the instruction as badly as a missing one. Duplications are harder to pin down than deletions, and a laboratory may check them with a second method.
Inversion
A section is flipped the wrong way round. Nothing is missing and nothing is added, so counting-based checks can miss it entirely. A known inversion in the MSH2 gene has been found in families with Lynch syndrome that earlier tests had cleared.
Insertion or move
A stretch of unrelated DNA lands inside a gene, or part of the gene is moved elsewhere. These are rare, can be hard to detect, and may need a specialist method or a wider test such as genome sequencing to find.
Often found by
- Specialist copy-counting methods
- Reading the RNA the gene makes
- Whole genome sequencing
Not sure whether this applies to you?
Ask an oncologistInside the laboratory
Why does ordinary sequencing struggle to see them?
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DNA is cut into short pieces
Modern sequencing breaks your DNA into many small fragments and reads each one separately. Each fragment is much shorter than most rearrangements.
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The pieces are matched back to a reference
Software lines each fragment up against a standard map of human DNA. A spelling mistake shows up clearly as a mismatch on the map.
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A missing section leaves no mismatch to see
If a whole section is deleted from one copy, the other copy still reads perfectly. Nothing looks misspelled. The only clue is that fewer fragments cover that stretch than expected.
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So the laboratory has to count
Finding a deletion or duplication means counting how much of each section is present and comparing it with normal samples. Some laboratories do this from the sequencing data, and others add a separate test such as MLPA.
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A suspected change is then confirmed
Because counting can be thrown off by poor-quality DNA, a suspected rearrangement is usually checked by a second method before it is reported.
On your report
The words you will meet, in plain language
- Large genomic rearrangement
- A fault involving a whole section of a gene rather than a single letter.
- Copy number
- How many copies of a stretch of DNA you have. Normally two, one from each parent.
- Deletion or duplication analysis
- The extra check that counts copies. Reports sometimes call it del/dup or CNV analysis.
- Exon
- One of the sections of a gene that carries instructions. Deletions are often described by which exons are missing.
- MLPA
- A laboratory method that counts the copies of each exon in a chosen gene. Often used to find or confirm a deletion.
- Pathogenic
- Known to cause disease. A confirmed deletion in a cancer gene is usually reported this way.
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Side by side
A spelling change and a rearrangement, compared
A spelling change
A large rearrangement
One letter or a few letters altered
A whole section missing, doubled or moved
Seen directly by standard sequencing
Needs counting or a specialist method
The commonest kind of inherited fault
Less common, varies by gene and population
Relatives tested for the same letters
Relatives tested for the same missing section
Being straight with you
What this page cannot tell you
It cannot tell you whether your own test looked for rearrangements. That depends on the laboratory, the year and the exact test ordered. The methods section of your report usually says, and if it does not, the laboratory can tell your counsellor.
It cannot tell you whether to be retested
An older negative result that did not include deletion and duplication analysis is not automatically wrong. Whether it is worth repeating depends on how strong your family history is and what has changed since. A genetic counsellor weighs those together with you.
It cannot read a result you already hold
If your report names a deletion or duplication, what it means for you and your relatives is a question for the counsellor who ordered the test. Please do not rely on an online search to interpret it.
Who this does not apply to
Most people have never had genetic testing and do not need it. This page matters mainly to families who were tested some years ago, whose history still looks strongly inherited, and whose report does not mention copy-number checks.
Commonly believed
Four things families assume, and what is actually true
"Our test was negative, so the family is clear."
A negative covers only what the test could see. If it did not look for missing or extra sections, a rearrangement may still be there. Ask what methods were used.
"A bigger panel will catch rearrangements."
The number of genes has nothing to do with it. What matters is whether the laboratory counted copies of each section. A small panel with that check can see more than a large one without.
"A deletion is less serious than a spelling mistake."
Both can switch a gene off. A confirmed deletion in a cancer gene is treated with the same seriousness as any other harmful fault in that gene.
"Modern tests find every kind of rearrangement."
Most now find common deletions and duplications well. Inversions and some insertions can still be missed, which is why a strong family history with a clear result stays under review.
Questions we are asked
Common questions about large rearrangements
How do I know if my test looked for rearrangements?
Look at the methods or limitations section of the report for words like deletion and duplication analysis, copy number, CNV or MLPA. If none appear, ask the laboratory directly, or ask your counsellor to find out for you. Older reports are the most likely to have left it out.
Which genes are most affected by rearrangements?
They can occur in any gene. In inherited cancer they are well described in BRCA1, in the genes behind Lynch syndrome, including a deletion near MSH2 in a gene called EPCAM, and in several others. Your counsellor can tell you which matter for your family's pattern.
Can a rearrangement be passed on like any other fault?
Yes. It sits in every cell from birth and is inherited in the same way as a spelling change. Each child of a carrier has the same chance of inheriting it as they would for any other dominant fault, and relatives can be tested for it.
Do I need a new sample to check for a rearrangement?
Sometimes not. Some laboratories can rerun the copy-number check on stored DNA from your original test. If that is not possible, a fresh blood sample is used. Ask the original laboratory whether it still holds your sample.
My relative who had cancer has died. Can they still be tested?
Possibly. A stored tissue block from an old biopsy or surgery can sometimes be tested, although copy-number checks on old tissue are harder and not always reliable. Your counsellor may suggest testing a living relative instead.
Is this the same as a chromosome test?
Not quite. A chromosome test looks at very large changes you could see under a microscope. Rearrangements inside a single gene are far smaller than that, so they need gene-level methods to find them.
Does this apply to tumour testing too?
Tumours also carry deletions and duplications, and tumour tests look for them to guide treatment. That is a separate question, covered on our targeted therapy pages. This page is about faults you were born with.
Where do I start if I think an old test missed something?
Find the old report and write down who in the family has had cancer since. Take both to a genetic counsellor or your oncologist. Call the CION helpline if you are not sure who to approach, and we will point you to the right clinic.
Your Specialists
Meet CION's oncologists. Bring your family history or genetic report to them.
Our medical oncologists see people with a strong family history of cancer, arrange genetic counselling and testing where it fits, and plan the checks that follow.
Medical Oncologist
Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
Medical Oncologist
Dr. Bharati Devi Gorantla
MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
Medical Oncologist
Dr. Owais Mohammed
MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
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Sources
- MedlinePlus Genetics — What kinds of gene variants are possible?
- National Cancer Institute — NCI Dictionary of Genetics Terms: Copy Number Variant
- GeneReviews (NCBI) — BRCA1/2 Hereditary Breast and Ovarian Cancer
- GeneReviews (NCBI) — Lynch Syndrome
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.
Keep reading
Related pages
Deletion and duplication analysisThe check that finds most rearrangementsMLPA testing explainedThe method laboratories use to count gene sectionsWhen an older negative test should be repeatedIf your test was done years agoNext-generation sequencing: how it actually worksWhy short-read sequencing sees some faults and not others
Talk to us
Wondering whether an old test looked for this?
Send us the old report and a note of who in the family has had cancer, and we will help you work out whether a further check is worth making. One helpline serves every CION centre.