Each entry links to the Cancer Dictionary entries where the marker comes up, so you can see the same marker in the context of different diseases.
EGFR
Gene mutationAlso called Epidermal growth factor receptor.
What it is
A receptor on the cell surface that tells cells to grow. Certain mutations leave it permanently switched on, so the cell keeps growing without being told to.
Why it is discussed
One of the largest targetable groups in lung cancer, with several generations of matched agents. Which specific mutation is present matters, because they do not all behave alike.
How it is tested
Sequencing of tumour tissue or plasma. Exon-level detail should be stated in the report.
Worth knowing. An EGFR alteration in one cancer does not carry the same meaning in another. In colorectal cancer, for example, the relevant question about the EGFR pathway is a different one entirely.
Discussed inGliomaHead and neckLung (NSCLC)
ALK
Fusion or rearrangementWhat it is
A gene that, when joined to a partner gene, produces a hybrid protein that drives growth.
Why it is discussed
A well-established targeted class exists for it. Because it is a rearrangement, it is a different kind of finding from a point mutation.
How it is tested
Fusion-capable sequencing, immunohistochemistry or fluorescence in situ hybridisation. A DNA panel that reads only point mutations can miss it.
Worth knowing. Ask whether the panel used actually reads fusions. This is the single most common way an actionable ALK finding is missed.
Discussed inLymphomaLung (NSCLC)PancreaticSarcoma
ROS1
Fusion or rearrangementWhat it is
Another gene that drives growth when fused to a partner.
Why it is discussed
Uncommon, but with an established targeted class. Worth looking for specifically.
How it is tested
Fusion-capable sequencing or in situ hybridisation.
Discussed inLung (NSCLC)
RET
Fusion or rearrangementWhat it is
A gene that can drive cancer either by fusing with a partner or, in some cancers, through a point mutation. The two are different findings in different diseases.
Why it is discussed
Selective targeted agents exist. In medullary thyroid carcinoma, a RET alteration also raises an inherited-risk question.
How it is tested
Fusion-capable sequencing for rearrangements; standard sequencing for point mutations.
Worth knowing. A germline RET alteration has consequences for relatives that a somatic one does not.
Discussed inBiliary tractGastricHead and neckLung (NSCLC)PancreaticThyroid
NTRK
Fusion or rearrangementAlso called NTRK1, NTRK2, NTRK3.
What it is
A family of genes that drive growth when fused to a partner gene.
Why it is discussed
Rare, but actionable across many cancer types rather than being tied to one. This makes it one of the clearest examples of treating by molecular finding rather than by organ.
How it is tested
Fusion-capable sequencing. RNA-based methods detect fusions more reliably than DNA alone.
Worth knowing. Because it is rare, it is often not looked for. In cancers with few other options it is specifically worth asking about.
Discussed inBiliary tractUnknown primaryColorectalGliomaHead and neckLung (NSCLC)PancreaticSarcomaThyroid
KRAS
Gene mutationWhat it is
A switch protein inside the cell. Mutations lock it in the on position.
Why it is discussed
One of the most common drivers in cancer. Historically hard to target, and now with agents directed at specific variants such as G12C. In colorectal cancer, KRAS status is used to determine whether a treatment class is appropriate at all.
How it is tested
Sequencing. The specific codon and substitution should be reported, not simply “mutated”.
Worth knowing. G12C, G12D and G12V are not interchangeable findings. A report saying only “KRAS mutant” is not enough to act on.
Discussed inCervicalColorectalLung (NSCLC)OvarianPancreatic
NRAS
Gene mutationWhat it is
A close relative of KRAS, working in the same pathway.
Why it is discussed
Relevant in colorectal cancer alongside KRAS, and a driver in melanoma.
How it is tested
Sequencing, usually as part of extended RAS testing.
Discussed inColorectalMelanomaOvarian
BRAF
Gene mutationWhat it is
A protein in the same growth pathway as RAS. The V600E change is the best-characterised alteration in it.
Why it is discussed
V600E has established targeted options across several cancers. Non-V600 alterations behave differently and generally do not carry the same evidence.
How it is tested
Sequencing, or immunohistochemistry for V600E in some settings.
Worth knowing. A report saying “BRAF mutation” without specifying the variant is not actionable. V600E and non-V600E are different findings.
Discussed inBiliary tractUnknown primaryColorectalGISTGliomaMelanomaLung (NSCLC)OvarianThyroid
HER2 / ERBB2
Copy number changeAlso called ERBB2, HER2.
What it is
A growth receptor. Cancers can carry extra copies of the gene, called amplification, or a mutation within it. These are two different findings.
Why it is discussed
One of the longest-established targets in oncology. Relevant in breast, gastric, biliary, colorectal, lung, endometrial and other cancers, though what counts as positive differs by cancer.
How it is tested
Immunohistochemistry and in situ hybridisation for amplification; sequencing for mutation.
Worth knowing. HER2 can be heterogeneous within a tumour and can change between the primary and a metastasis. A negative result on a small biopsy is not always the last word.
Discussed inBiliary tractBladderBreastUnknown primaryCervicalColorectalEndometrialGastricHead and neckLung (NSCLC)Oesophageal
MET
Gene mutationWhat it is
A growth receptor. Two distinct alterations matter: exon 14 skipping, which is a splicing change, and amplification, which is extra copies.
Why it is discussed
Both have targeted options, and they are separate questions. Amplification also arises as a resistance mechanism to other targeted agents.
How it is tested
Sequencing for exon 14 skipping; copy number analysis for amplification.
Worth knowing. Exon 14 skipping and amplification are not the same finding and should be reported separately.
Discussed inBiliary tractUnknown primaryCervicalColorectalGastricGliomaLiver (HCC)Kidney (RCC)MelanomaMyelomaLung (NSCLC)Ovarian
FGFR2 and FGFR3
Fusion or rearrangementAlso called FGFR1, FGFR.
What it is
A family of growth receptors. They can be altered by point mutation, fusion or amplification depending on the cancer.
Why it is discussed
FGFR2 fusions in biliary tract cancer and FGFR3 alterations in urothelial cancer both have dedicated targeted classes.
How it is tested
Sequencing that reads fusions as well as point mutations.
Worth knowing. Acquired resistance mutations within FGFR are well described, which is why retesting at progression is discussed.
Discussed inBiliary tractBladderGastricGliomaLiver (HCC)Oesophageal
BRCA1 and BRCA2
Gene mutationWhat it is
Genes responsible for a high-fidelity form of DNA repair. When they fail, cells depend on other, more error-prone repair routes.
Why it is discussed
Relevant in two separate ways. As a tumour finding they can open a specific treatment class. As an inherited finding they carry risk information for the whole family.
How it is tested
Sequencing of tumour tissue for somatic findings, and of blood or saliva for germline findings. These are different tests.
Worth knowing. A tumour panel reporting a BRCA alteration does not establish that it is inherited. Confirming that requires a separate germline test, and the answer matters to relatives.
Discussed inBiliary tractBreastOvarianPancreaticProstate
PALB2, ATM and other repair genes
Gene mutationAlso called ATM, PALB2, CHEK2, RAD51.
What it is
Other genes in the same DNA repair machinery as BRCA1 and BRCA2.
Why it is discussed
They contribute to the same functional state, though the strength of evidence varies considerably between genes.
How it is tested
Included on comprehensive tumour panels and on germline panels.
Worth knowing. Not all repair genes carry equal evidence. PALB2 is better established than several others, and a finding in a less-studied gene is not equivalent.
Discussed inBreastCMLEndometrialGastricGliomaHead and neckLiver (HCC)MelanomaPancreaticProstateLung (SCLC)
HRD
Genomic signatureAlso called Homologous recombination deficiency.
What it is
A measurement of the genomic damage left behind when high-fidelity DNA repair has been failing. A scar, rather than the cause of the scar.
Why it is discussed
It captures repair failure arising from causes other than a BRCA alteration, so it can identify tumours a gene-by-gene look would miss.
How it is tested
A broad genomic assay, reported as a score against a threshold.
Worth knowing. Different assays measure it differently and thresholds are not interchangeable. Which assay produced a score matters.
Discussed inOvarian
MMR and MSI
Genomic signatureAlso called Mismatch repair, Microsatellite instability, dMMR, MSI-high.
What it is
A DNA proofreading system. When it fails, characteristic errors accumulate in short repeated stretches of DNA, which is what microsatellite instability measures.
Why it is discussed
One of the clearest tumour-agnostic markers in oncology: the finding carries meaning across cancer types rather than only in one. It is also the main route by which Lynch syndrome is discovered.
How it is tested
Immunohistochemistry for the four repair proteins, PCR-based microsatellite testing, or sequencing-based MSI scoring.
Worth knowing. Mismatch repair deficiency has two possible causes: an inherited condition, or a much more common non-inherited switching off of the gene. Distinguishing them matters for the family, and requires further testing.
Discussed inBiliary tractBladderBreastUnknown primaryCervicalColorectalEndometrialGastricOesophagealOvarianPancreaticProstate
TMB
Genomic signatureAlso called Tumour mutational burden.
What it is
A count of how many mutations a tumour carries, expressed per million bases of DNA read.
Why it is discussed
Discussed in the immunotherapy conversation, on the reasoning that more mutations means more abnormal proteins for the immune system to recognise.
How it is tested
Requires a broad panel. Small panels cannot estimate it reliably.
Worth knowing. Panel size and the bioinformatic method both change the number. A TMB value from one assay is not directly comparable with one from another, and it is a weaker predictor in some cancers than others.
Discussed inBladderUnknown primaryCervicalColorectalHead and neckMelanomaNasopharyngealLung (NSCLC)Lung (SCLC)
PD-L1
Protein expressionWhat it is
A protein on the surface of tumour and immune cells that acts as a brake on the immune response.
Why it is discussed
Used to inform immunotherapy decisions in several cancers.
How it is tested
Immunohistochemistry on tissue. It is not reported by a genomic panel, and requesting sequencing does not produce it.
Worth knowing. Scoring differs by cancer and by assay: a combined positive score in gastric cancer is not the same measurement as a tumour proportion score in lung cancer. The threshold that matters depends on the treatment being considered.
Discussed inBladderUnknown primaryCervicalGastricHead and neckLiver (HCC)NasopharyngealLung (NSCLC)Oesophageal
TP53
Gene mutationWhat it is
A gene whose normal job is to stop damaged cells from dividing. It is the most commonly altered gene in cancer.
Why it is discussed
Usually descriptive rather than directly actionable, but it carries substantial weight in some diseases, particularly the leukaemias, lymphomas and myeloma, where it shapes the treatment discussion directly.
How it is tested
Sequencing. In some diseases, loss of the region containing it is assessed separately as del(17p).
Worth knowing. A germline TP53 alteration means Li-Fraumeni syndrome, which is a serious family finding. A somatic one does not.
Discussed inALLAMLBladderCLLEndometrialGliomaHead and neckLiver (HCC)LymphomaMyelomaMDS and MPNNasopharyngeal
PIK3CA and the PI3K pathway
Gene mutationAlso called AKT1, PTEN.
What it is
A growth-signalling pathway. PIK3CA mutation, AKT1 mutation and PTEN loss all activate it by different routes.
Why it is discussed
Relevant in breast, gynaecological and several other cancers.
How it is tested
Sequencing for mutations; sequencing or immunohistochemistry for PTEN loss.
Discussed inBreastCervicalColorectalEndometrialHead and neckProstate
ESR1
Gene mutationWhat it is
The gene for the oestrogen receptor. Mutations in it change the receptor so it stays active without oestrogen.
Why it is discussed
A recognised mechanism of acquired resistance to endocrine treatment in breast cancer.
How it is tested
Sequencing, and particularly well suited to plasma testing because the mutation may be present in only part of the disease.
Worth knowing. It is usually absent at diagnosis and appears under treatment. Testing archival tissue from the original diagnosis will not find it. The sample has to be taken at progression.
Discussed inBreast
IDH1 and IDH2
Gene mutationWhat it is
Metabolic enzymes. Mutations change what they produce, which alters how genes are switched on and off across the cell.
Why it is discussed
Central to how adult gliomas are classified, and directly targetable in glioma, acute myeloid leukaemia and biliary tract cancer.
How it is tested
Sequencing, or immunohistochemistry for the most common glioma variant.
Discussed inAMLBiliary tractGlioma
KIT and PDGFRA
Gene mutationAlso called PDGFRA.
What it is
Two related growth receptors. Activating mutations in them drive gastrointestinal stromal tumours, and KIT alterations also occur in some melanomas.
Why it is discussed
Which gene, and which exon within it, changes the treatment discussion directly.
How it is tested
Sequencing, with exon-level reporting.
Worth knowing. The PDGFRA D842V variant behaves differently from every other alteration in that gene. A report that names only the gene is not enough.
Discussed inAMLGISTMelanoma
BCR::ABL1
Fusion or rearrangementAlso called Philadelphia chromosome.
What it is
A fusion gene created when parts of two chromosomes join. It produces a permanently active growth signal.
Why it is discussed
It defines chronic myeloid leukaemia and a group of acute lymphoblastic leukaemia, and it is the historical starting point for targeted cancer therapy.
How it is tested
PCR and cytogenetic testing. Quantitative monitoring is reported on an international standardised scale.
Worth knowing. At resistance, the specific kinase domain mutation matters, and T315I in particular changes which agents can work.
Discussed inALLCML
FLT3 and NPM1
Gene mutationAlso called NPM1.
What it is
Two genes altered in acute myeloid leukaemia. FLT3 is a growth receptor; NPM1 is a nuclear protein.
Why it is discussed
FLT3 is directly targetable, and NPM1 both classifies risk and serves as the best marker for tracking residual disease in that leukaemia.
How it is tested
Sequencing and PCR-based methods, prioritised for speed because they change the first treatment given.
Worth knowing. These results are needed within days in acute leukaemia, not weeks. Turnaround is part of the clinical question.
Discussed inAML
ctDNA
Functional or response measureAlso called Circulating tumour DNA, Liquid biopsy.
What it is
Fragments of tumour DNA shed into the bloodstream, readable from an ordinary blood draw.
Why it is discussed
It allows profiling when tissue is unavailable, and allows the same question to be asked repeatedly over time, which tissue biopsy cannot.
How it is tested
Sequencing of plasma. Sensitivity depends on how much tumour DNA is present.
Worth knowing. A “not detected” result does not mean the cancer is absent. It may mean the tumour is shedding little DNA. How much shedding is expected varies enormously by cancer type and by disease burden.
Measurable residual disease
Functional or response measureAlso called MRD, Molecular residual disease.
What it is
Disease remaining after treatment at a level below what a scan or a microscope can detect.
Why it is discussed
It is the most informative single measurement in several leukaemias, and is under active study in solid tumours after curative-intent treatment.
How it is tested
Flow cytometry or molecular methods in leukaemia; ctDNA-based assays in solid tumours, often designed around the individual tumour’s own mutations.
Worth knowing. In solid tumours the central question is still being answered: detecting recurrence earlier is established, but whether acting earlier improves outcomes is what trials are testing. Worth asking what would actually be done with a positive result.
Discussed inALLAMLMyeloma
HPV
Viral markerAlso called Human papillomavirus, p16.
What it is
A common virus. Persistent infection with high-risk types causes nearly all cervical cancer and a large share of oropharyngeal cancer.
Why it is discussed
In the oropharynx it defines a biologically distinct disease with a substantially better outlook. It is also the basis of prevention through vaccination and screening.
How it is tested
p16 immunohistochemistry as a practical surrogate, and direct HPV testing. Circulating HPV DNA in blood is under study for surveillance.
Worth knowing. p16 is a surrogate and not identical to HPV status. Outside the oropharynx it is less reliable as a proxy.
Discussed inCervicalHead and neck
EBV
Viral markerAlso called Epstein-Barr virus.
What it is
A common virus that most people carry harmlessly, but which is causally linked to nasopharyngeal carcinoma, some gastric cancers and several lymphomas.
Why it is discussed
In nasopharyngeal carcinoma, circulating EBV DNA is one of the most established blood-based tumour markers anywhere in solid oncology.
How it is tested
Tumour testing for viral presence, and quantitative measurement of circulating viral DNA in blood.
Discussed inGastricLymphomaNasopharyngeal
Nectin-4, TROP-2, DLL3 and other surface targets
Protein expressionAlso called Nectin-4, TROP-2, DLL3, Claudin 18.2, BCMA, Mesothelin, PSMA.
What it is
Proteins sitting on the outside of cancer cells. They are addresses rather than drivers: the cancer does not depend on them, but they let a treatment find the cell.
Why it is discussed
They underpin antibody-drug conjugates, cell therapies and radioligand approaches, which deliver a payload to cells carrying the marker.
How it is tested
Immunohistochemistry for most; imaging for PSMA and somatostatin receptors. Not reported by genomic sequencing.
Worth knowing. Expression can be lost under treatment, which is a recognised resistance mechanism. Reassessment at progression is often discussed.
Discussed inALLBladderGastricLymphomaMesotheliomaMyelomaNeuroendocrineOesophagealProstateLung (SCLC)
Fusions and rearrangements, as a class
Fusion or rearrangementWhat it is
Any finding where two genes have been abnormally joined, or a chromosome segment has moved.
Why it is discussed
Fusions are among the most actionable findings in oncology, and in several sarcomas and leukaemias they define the diagnosis itself.
How it is tested
RNA-based sequencing, fusion-capable DNA panels, fluorescence in situ hybridisation or cytogenetics, depending on the setting.
Worth knowing. This is the single most important question to ask about any genomic panel: does it read fusions? Many do not, and a negative result from a panel that cannot detect them is not evidence of absence.
Discussed inALLAMLBiliary tractUnknown primaryColorectalGISTGliomaHead and neckKidney (RCC)LymphomaLung (NSCLC)Oesophageal
