Medical Oncologist
Biomarker & Molecular Testing
Which Cancers Always Need — Mutation Testing?
For several cancers, the right treatment depends directly on what mutations the tumour carries. Testing is done on the biopsy tissue you have already had — and for the cancers on this page, ASCO, ESMO and NCCN guidelines say it should happen before systemic treatment begins.
Medically reviewed by Dr. T. Raghavender Reddy, Medical Oncologist, MBBS · DM (Medical Oncology) · MD (Radiation Oncology) · Last reviewed August 2026
- Not just one cancer type — Lung, bowel, breast, ovarian, gastric and bile duct cancers are all on the standard testing list.
- Your existing biopsy is usually enough — Most mutation testing is done on the sample from your biopsy — you usually do not need a new procedure.
- Results change the treatment decision — A found mutation may open a targeted therapy option. An absent one also shapes the plan.
- Any tumour can carry an MSI marker — MSI-H status qualifies for immunotherapy consideration regardless of which organ the cancer started in.
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Lung, colorectal, breast, ovarian, gastric and biliary cancers are almost always tested for mutations before treatment begins. So is any tumour showing signs of microsatellite instability, regardless of where it started. The mutations found — or not found — directly shape which treatments your oncologist is able to offer you.
Why do some cancers always need testing before treatment starts?
Treatment choices for several cancers now depend on the molecular profile of your specific tumour, not just its type.
For lung cancer, knowing whether EGFR, ALK or KRAS is altered changes what the first medicine your oncologist considers. For colorectal cancer, a KRAS result determines whether a whole class of drugs can be used at all. The cancer type alone is no longer enough information.
Testing is done on tissue removed during your biopsy — you usually do not need another procedure. How long results take depends on what is being tested. Basic protein staining, such as HER2 or PD-L1, is typically faster. Full next-generation sequencing panels that look across many genes take longer. Ask your team when to expect your specific results.
If your diagnosis is on the checklist below and testing has not been mentioned, it is reasonable to ask your oncologist directly.
Which cancers are almost always tested?
- Non-small cell lung cancerEGFR, ALK, ROS1, KRAS, BRAF, MET exon 14, PD-L1 — all standard before first-line treatment begins
- Colorectal cancerKRAS, NRAS, BRAF, MSI/MMR status, HER2 — results affect which drugs can and cannot be used
- Breast cancerHER2, BRCA1/2, PIK3CA (in hormone receptor-positive), PD-L1 (in triple-negative)
- Ovarian cancerBRCA1/2 and homologous recombination deficiency (HRD) — guides maintenance therapy decisions after response
- Gastric and gastroesophageal cancerHER2, PD-L1, MSI, FGFR2 — tested at diagnosis and sometimes again at progression
- MelanomaBRAF V600 — determines whether a targeted therapy combination is available as an option
- Cholangiocarcinoma (bile duct cancer)FGFR2 fusions, IDH1, BRAF, HER2, MSI — specific approved targeted agents exist for several of these
- Medullary thyroid cancerRET mutations — targeted therapy is available for both sporadic and inherited RET alterations
- Pancreatic cancerBRCA1/2, ATM, mismatch repair status — guides platinum use and PARP inhibitor discussion
- Any solid tumourMSI-H / dMMR status — qualifies for immunotherapy consideration regardless of cancer type, per NCCN guidance
What does a result actually change? A diagnosis-by-diagnosis guide
| Cancer type | If a targetable mutation is found | If no targetable mutation is found |
|---|---|---|
| Non-small cell lung | Targeted therapy is usually preferred as first-line treatment over chemotherapy | PD-L1 level guides whether immunotherapy alone, or combined with chemotherapy, is considered |
| Colorectal | KRAS/NRAS wild-type: anti-EGFR agents may be added. MSI-H: immunotherapy considered | BRAF-mutated: specific drug combinations apply; chemotherapy backbone continues |
| Breast | HER2-positive: anti-HER2 therapy added. BRCA-mutated: PARP inhibitor discussed | Hormone receptor status, stage and menopausal status guide the plan |
| Ovarian | BRCA-mutated: PARP inhibitor maintenance may be offered after platinum response | HRD-positive but BRCA wild-type: some PARP inhibitors may still apply — discuss with your oncologist |
| Gastric | HER2-positive: targeted agent added. MSI-H: immunotherapy considered as first-line | Chemotherapy combination is the standard starting point |
| Melanoma | BRAF V600E: targeted combination therapy is available | Immunotherapy is the standard first approach whether or not BRAF is found |
| Cholangiocarcinoma | FGFR2 fusion or IDH1 mutation: specific approved agents available | Chemotherapy is standard; clinical trials are worth discussing |
| Any solid tumour | MSI-H or dMMR: immunotherapy may be considered regardless of where the cancer started | Treatment follows the standard approach for the organ of origin |
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What happens if treatment starts without mutation testing?
Starting without results is not always avoidable — some situations are urgent. But for the cancers on this list, it can mean beginning with chemotherapy when a targeted option might have been the better first choice.
Some targeted therapies are most effective when given as the first treatment rather than after chemotherapy. A delay in testing can become a delay in the option itself — and occasionally the option closes.
If testing was not done at your original diagnosis, ask whether stored biopsy tissue can still be used. Laboratories can often work from samples fixed and preserved at the time of surgery, without needing a new procedure.
Did you know?
A tumour found to be MSI-H (microsatellite instability-high) may qualify for immunotherapy regardless of which organ it started in — bowel, stomach, womb, pancreas or another site entirely.
NCCN guidelines describe this as a tumour-agnostic indication: the test result, not the diagnosis, is what determines eligibility for this class of treatment.
Source: NCCN Clinical Practice Guidelines in Oncology — Tumour Mutational Burden-High or Microsatellite Instability-High Cancer
Questions about mutation testing — answered
What if my biopsy sample is too small for testing?
A sample too small for full molecular testing is more common than it should be, especially if a core needle biopsy was done rather than a surgical resection. Your oncologist may request a repeat biopsy of the primary tumour or a metastatic site. In some situations, liquid biopsy — a blood test that detects fragments of tumour DNA circulating in the bloodstream — can provide some of the same information without a new tissue procedure. Liquid biopsy is not a complete substitute for tissue testing in all cases, but it is a useful option when tissue is unavailable or a repeat procedure would carry significant risk.
How long does mutation testing take?
It depends on what is being tested. Basic protein staining tests — such as PD-L1 immunohistochemistry or HER2 scoring — are typically done alongside standard pathology and available relatively quickly. A broader next-generation sequencing panel that looks at dozens or hundreds of mutations simultaneously takes longer. Some results can be expedited when treatment planning is urgent. Ask your oncologist which tests have been ordered, what they are looking for, and when results are expected — that timeline should be part of your treatment plan, not something you have to chase separately.
Is mutation testing an additional cost on top of pathology?
Basic tests such as HER2 staining and PD-L1 scoring are generally included as part of standard diagnostic pathology for the cancers where they are clinically required. Broader molecular panels — particularly next-generation sequencing across many genes simultaneously — usually carry an additional cost. Any cost figure is indicative and changes over time; ask the laboratory or your care team for a written estimate before proceeding. In some cases your oncologist may be able to recommend a panel that covers the clinically necessary markers without ordering the broadest available option, which can reduce the cost without affecting the treatment decision.
What if a mutation is found but no approved drug exists for it?
Not every actionable mutation has an approved drug available in India. When that happens, your oncologist may discuss a clinical trial testing an agent for that target, a compassionate use or early access programme, or referral to a centre with access to basket trials — trials that enrol patients based on the mutation rather than the cancer type. A multidisciplinary tumour board review is worth requesting in this situation, because the answer to what is available changes as new approvals emerge, and a second centre may have access to options your current centre does not.
Is this the same as genetic testing to check if my family is at risk?
No, and the difference matters. Mutation testing on your tumour looks at the cancer cells themselves — changes that arose in your lifetime, usually in that tissue alone, and not passed to children. This is called somatic testing. Germline genetic testing, done on your blood or saliva, looks for mutations you were born with and that your children could inherit — such as an inherited BRCA1 or BRCA2 variant. Some tests order both from the same biopsy sample; others test only the tumour. Ask your oncologist which type was done and whether germline testing is recommended given your personal and family history.
Can testing be repeated if the cancer comes back or spreads?
Yes, and in many situations it should be. Tumours can change their molecular profile over time, particularly after treatment — a cancer that had no actionable mutation at diagnosis may develop one at relapse, or lose a mutation it carried before. For several cancer types, ESMO and NCCN guidelines recommend retesting at progression, especially when a targeted option is being considered. Retesting at progression also allows your oncologist to understand whether resistance has developed to a previous targeted therapy, and which next-line options are most likely to work given the current profile of the disease.
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Common questions
Frequently asked questions
Do all cancer patients need mutation testing?
No. Mutation testing is recommended for specific cancer types where the result changes the treatment decision. For some early-stage cancers where surgery alone is the treatment, molecular testing may not affect the immediate plan. For haematological cancers, the testing approach differs significantly from solid tumour testing. Your oncologist is the right person to explain whether it applies to your specific diagnosis and stage — and if you are unsure, asking directly is always reasonable.
What is the difference between mutation testing and a PET-CT scan?
A PET-CT scan shows where cancer is in the body and how active it is — it is an imaging test. Mutation testing analyses the DNA of your tumour cells to find specific molecular changes. The two tests answer different questions. PET-CT tells your team where the cancer is and how far it has spread. Mutation testing tells them which molecular targets are present and which treatments are likely to work. Most patients with the cancers listed on this page will have both at some point in their diagnosis and treatment planning.
What does it mean if no mutation is found?
A negative result — no actionable mutation found — is information, not bad news in itself. It tells your oncologist which treatments are unlikely to help and which standard options to prioritise. For lung cancer, for example, a negative EGFR result shifts attention to PD-L1 status and the role of immunotherapy. A result of 'no mutations found' on a limited panel does not mean no mutations exist — a broader panel or liquid biopsy may find something a smaller test missed. Ask your oncologist what was tested and whether further testing is worth considering.
Can the same biopsy sample be used for multiple tests?
Usually, yes — within limits. Pathology laboratories are experienced at working with limited tissue and will divide the sample across the tests requested. The constraint is the amount of material available. Very small samples, particularly from fine-needle aspirates, may not have enough tissue for both standard pathology and extended molecular testing. If tissue is limited, your oncologist will prioritise which tests matter most for your treatment decision. When a biopsy is being planned, it is worth ensuring your oncologist knows that molecular testing may be needed so enough material is taken.
Is liquid biopsy as accurate as testing the tumour tissue directly?
For some mutations and some cancer types, liquid biopsy results closely match tissue testing. For others — particularly when the tumour is small or early stage, or when little tumour DNA is circulating in the blood — a liquid biopsy may miss mutations that tissue testing would have found. Liquid biopsy is most useful when tissue is unavailable, when a repeat procedure would carry significant risk, or when monitoring a known mutation during treatment. ESMO guidance supports its use in specific clinical situations. In most settings it is a complement to tissue testing, not a replacement.
Should I ask for my mutation test results in writing?
Yes, and it is entirely reasonable to request them. Having the report means you can share it accurately if you seek a second opinion, refer to it if your treating team changes, and understand exactly which mutations were tested and which were not. The report will show which genes were analysed, which variants were found, and whether they are classified as actionable, of uncertain significance, or benign. If the language is unclear, ask your oncologist to explain the findings that affect your treatment plan — that part should be in plain language before any treatment decision is made.