Comprehensive Genomic Profiling: Who It May Suit and What the Report Can Tell You

What is comprehensive genomic profiling?

Cancer gene testing is a phrase patients hear constantly, and it is used for several quite different tests. This article, prepared by the YOUNIFY Clinic medical team, separates them out: what comprehensive genomic profiling (CGP) is, how it differs from older single-gene testing, who it may suit, what the report genuinely tells you, and just as importantly what it cannot. For the wider picture, see what precision oncology is and our precision oncology service.

CGP reads the genetic sequence of a tumour across hundreds of genes in one test, using NGS (next-generation sequencing). The purpose is to identify alterations that may inform the choice of treatment.

One distinction matters from the outset. CGP examines the genetics of the cancer cells. It is not a test of the patient's inherited genetics to predict whether they will develop cancer in future. These are different tests, with different purposes and different interpretation.

The alterations CGP typically looks for include:

• Point mutations and small insertions or deletions — small changes in the genetic code, such as those seen in EGFR, BRAF and KRAS
• Gene fusions — two genes joined abnormally, as seen with ALK, ROS1, RET and NTRK
• Copy number alterations — extra or missing copies of a gene, such as HER2 or MET amplification
• Immune-side biomarkers — MSI (microsatellite instability) and TMB (tumour mutational burden), alongside PD-L1 protein staining, which is usually performed by a separate method

CGP compared with single-gene testing

Older testing looks at one gene, or a few hotspots, in response to a specific clinical question. It uses less tissue and returns faster. CGP reads hundreds of genes at once, giving a broader picture, but it needs more tissue, takes longer, and produces information that has to be interpreted by a team.

Choosing between them is not a question of which is superior. It is a question of what the clinical question is right now, how much tissue exists, and how much time there is before a decision has to be made.

What the report can and cannot tell you

A CGP report usually divides findings into several groups, and not all of them can be used to select a drug. This distinction is worth understanding, because a report running to many pages does not mean many treatment options exist.

1. Actionable alterations. This is the group that most affects decisions, for example findings involving EGFR, ALK, ROS1, RET, NTRK, BRAF, HER2 or MET in the appropriate disease context. Finding a target does not automatically mean the matched drug suits that person; tumour type, stage, previous treatment and general fitness all still weigh in. How each drug class works is covered in targeted therapy and immunotherapy basics.

2. Biomarkers considered for immunotherapy — MSI, TMB and PD-L1. These inform a decision but none of them predicts perfectly. Someone with a seemingly favourable value may not respond, and the reverse also happens.

3. Variants of uncertain significance (VUS). These appear frequently. A real change in a gene has been found, but current evidence is not sufficient to say what it means. A VUS should not be used to choose treatment and should not be read as either bad news or good news.

4. Possible germline findings. Tumour testing sometimes shows a pattern suggesting the alteration may also be present in normal cells. That has to be confirmed with a dedicated germline blood test alongside genetic counselling, because it has implications for first-degree relatives.

5. No actionable target found. This is an ordinary result. Not every tumour carries a genomic alteration for which a targeted drug exists. Standard treatment options remain to be considered, and the information is still useful in ruling out approaches unlikely to help.

Reading all five groups against the clinical context is the job of a molecular tumour board, rather than of any one person reading line by line.

Biomarkers commonly considered by tumour type

No biomarker is relevant to every cancer. The list below is a broad educational overview of why different patients are sent for different tests. It is not a testing protocol.

• Lung cancer — EGFR, ALK, ROS1, BRAF, RET, MET, NTRK and KRAS are commonly considered, along with PD-L1
• Colorectal cancer — KRAS, BRAF, HER2 and MSI status
• Breast cancer — HER2 together with hormone receptors, and in some settings germline information
• Gastrointestinal cancers (stomach, oesophagus, pancreas, liver and biliary tract) — HER2, MSI, TMB and other organ-specific alterations
• Prostate cancer — DNA repair related findings, and MSI status in some settings

Selecting the panel that fits the disease and the situation is the treating team's responsibility, not something a patient should decide from information found online.

Who this test may suit

CGP is generally considered for people who already have a cancer diagnosis and a clinical question that the result could genuinely change. Testing without a question behind it rarely alters a plan.

• Advanced or metastatic disease, with the next line of treatment being planned
• Disease progressing on current treatment, where other genomically defined options are being considered
• Focused testing already done and negative, although the clinical picture still suggests a target may exist
• Rare cancers, or cancer of unknown primary origin
• Considering a clinical study that uses molecular criteria for eligibility

Who this test is not designed for: people who do not have a cancer diagnosis. CGP is not a screening test for the general population, it cannot tell you whether you will develop cancer, and an unremarkable report does not mean a person is free of disease.

Limitations you should know

Patient, family and medical team should agree on these limits before anything is arranged, so that expectations match what the test can actually do. For patients travelling from abroad, one further practical point applies: existing pathology blocks usually have to be requested from the original hospital, and that request can take longer than the test itself.

• Not every tumour carries a genomic alteration for which a targeted drug exists.
• Tissue may be insufficient or of inadequate quality, requiring a fresh sample or a switch to blood-based testing.
• Archived tissue may no longer reflect the current disease, because tumours change over time and with prior treatment.
• A tumour may differ genomically between sites (tumour heterogeneity), so sampling one site may not represent all of it.
• Many findings are variants of uncertain significance and cannot yet be used to decide treatment.
• Even when a matched target is found, no one can predict in advance whether an individual will respond. Outcomes vary from person to person.
• Findings with implications for first-degree relatives may emerge, so genetic counselling should be available when indicated.
• This test is not a reason to stop or delay treatment you are currently receiving. Decide together with the oncologist treating you and do not adjust or stop existing treatment on your own.

Where tissue is scarce or very old, blood-based testing may be an option; see liquid biopsy and ctDNA.

Costs depend on which tests are used and on the treatment plan. The medical team will assess and explain all costs in full before anything begins.

What to expect at YOUNIFY

At YOUNIFY Clinic, CGP begins with a clear clinical question: how would this result change the decision? If the honest answer is that it would not, the medical team says so rather than sending the test.

• 1. Consultation and review of existing documents — pathology, special stains, imaging and treatment history, including reports from your hospital abroad.
• 2. Checking the available sample — whether the archived block holds enough material and a sufficient proportion of tumour cells.
• 3. Choosing how to sample — archived tissue, a fresh biopsy, or blood-based testing instead of or alongside it.
• 4. Explanation before consent — what the test can and cannot answer, the real possibility of no target being found, and what happens if something with family implications appears.
• 5. Molecular tumour board review — the report interpreted alongside the clinical picture.
• 6. Going through the result with patient and family — section by section, in plain language, with the options available and what remains unknown.

If the plan calls for chemotherapy, radiotherapy, cancer surgery or any intravenous treatment, the medical team arranges a coordinated referral to a partner facility.

If you are weighing up whether genomic profiling is worth doing, and want to understand what it would change, you can read about our precision oncology service or contact the medical team on WhatsApp at +66 81 556 9696. Please take whatever you learn back to the oncologist treating you, and continue your current treatment unless they advise otherwise.