How is cancer diagnosed? - Molecular HealthMolecular Health

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How is cancer diagnosed?

Cancer is a complex disease. Whether you develop cancer is defined by your unique genomic variants – but also by environmental factors, lifestyle factors, and other factors we don’t yet understand.

Should I have a molecular diagnostic test?

The answer is simple: yes.


There is an increasing appreciation of the potential that tumor profiling has to help physicians to find the best cancer treatment for individual patients based on genomic variants, regardless of age, ethnicity, and family history.

 

Molecular diagnostic tests Molecular diagnostic testsAlso called genomic tests, genomic profiling, genetic tests, or molecular diagnostics, are medical diagnostic tests that check whether variations (variants) are present in a person’s genetic code (genome) that tell physicians about the type of cancer they have and how their disease may react to specific drugs. This combination of gene and drug information is called biomarker, from biological + marker. can make a real difference in improving the outcomes for individual patients. Researchers have identified many treatment-relevant variants, and the speed of discovery is increasing. Medical professionals such as oncologists, radiologists, geneticists, and surgeons come together in regular meetings (tumor boards) to discuss the best care options for their patients. The physicians gain valuable information about a patient’s cancer from the list of variants involved in it. They may discover that a drug is available that is known to target these variants and stop them from reproducing. This targeted therapy may make it more likely that the tumor shrinks, which would increase life expectancy and improve quality of life.

This is called personalized medicine, or precision medicine.

 

Personalized medicine is a new field in which physicians use genomic diagnostic tests genomic diagnostic testsAlso called genomic tests, genomic profiling, genetic tests, or molecular diagnostics, are medical diagnostic tests that check whether variations (variants) are present in a person’s genetic code (genome) that tell physicians about the type of cancer they have and how their disease may react to specific drugs. This combination of gene and drug information is called biomarker, from biological + marker. to find the medication that will work best for each patient.

 

 

A genomic test may identify a variant in the cancer that will respond to targeted therapy. It may find a variant that means a standard prescribed treatment would be ineffective, so that a patient can avoid it, saving money and reducing unpleasant side effects. It may find out that a specific medication would be toxic for a patient, causing harm rather than healing. Or it might discover that there is a clinical trial testing a promising new treatment focused on the cancer’s genomic profile.

    1. Your physician explains the test and you sign a form stating that you understand it. This is called informed consent.
    2. A sample is taken from the tissue of your tumor. This can be from a biopsy biopsyThis is a procedure by which your physician collects a small sample of cells from your cancer for testing in the lab. Depending on the cancer type, the cells are either taken from the tumor itself, or from bone marrow, or from skin. Samples from blood are only possible for blood cancers.
      or a resection resectionA procedure by which tissue is surgically removed from your body, for example, to remove all or part of a tumor. Cells can then be collected from the tumor for testing in the lab.. For some cancers, samples from a blood test (liquid biopsy) can be used. In these cases, tumor cells or tumor DNA circulating in the blood are used in the genomic analysis.
    3. Your physician orders the test and the sample is prepared for transport by the hospital lab.
    4. The sample is sent to a CLIA-certified genomic testing lab where the genomic patterns in your tumor are decoded (sequenced). This technique is called next-generation sequencing (NGS). From these data, genomic variants are identified.
    5. The genomic test results are analyzed and interpreted, for example, with MH Guide. MH Guide compares the thousands of variants in your tumor to information published in hundreds of scientific papers – a task that could never be done by a human – and identifies any significant variants and associated treatment options.
    6. An MH Guide report is finalized by a specialist, for example, a molecular pathologist. It lists the most important matches between your genomic profile and up-to-date knowledge about medicine, and a summary of what drugs are available to treat your cancer.
    7. Your treating physician receives the MH Guide report and uses the results of the analysis to make an evidence-based final decision on the best medication for you.

If your treating physician recommends a molecular diagnostic test in your case, they will be able to inform you about reimbursement by your medical insurance. However, until genomic tests become mainstream, you should double-check with your health insurance company about coverage in your case.

Once your physician knows the molecular profile of your cancer, you can ask whether there are any clinical trials recruiting patients with your disease and your tumor’s genomic profile. Clinical trials are expensive to run, so you know that the medication being tested in the trial has already gone through years of research in labs, and the sponsoring company believes the drug has the potential to be better than other drugs already on the market. Taking part in a clinical trial may take up more of your time, requiring extra tests to monitor your disease and any side effects, but it may be financially interesting, if the company sponsoring the trial covers the costs of the drug being tested. In addition, in most cases clinical trials are the only way to get access to treatments with innovative cancer drugs that are not yet available on the market.

Understanding the genomic test report

The report lists the variants causing your cancer and the medication that is known to target these variants To see a sample report, click here.


A variant can cause cancer by damaging a protein – but variants also make the cancer vulnerable, by telling us which medication the cancer will respond to.


Most relevant variants are found on DNA segments called exons, which are the parts of genes from which proteins are built. Genes are located on chromosomes, and the sum of all the chromosomes in a cell is called the genome. Scientists can describe each of the positions in the genome, but only the variant name gives us information that is specific enough to base a medical decision on it. Each variant has a unique name, following standardized rules. The first part of the variant name is the gene name on which it is found. The second part tells us more about the variant.


There are three main forms of variant: substitutions (e.g., SNVs), insertions and deletions (e.g., indels), and structural variants (e.g., fusion genes or copy number alterations).

Different variants are known to play a role in different cancer types, and the variants involved in hereditary cancers and in non-hereditary cancers are also different.

Variants in which one nucleotide is changed are called single nucleotide variants (SNVs). An example of a SNV is EGFR p.T790M (this tells us that the amino acid Threonine is swapped for Methionine at position 790).

If a small number of nucleotides are added, deleted, or exchanged, these are called insertions (ins), or deletions (del), or insertion-deletions (indel). An example is EGFR p.E746_A750del (this tells us that the region from 746 to 750 is deleted), another example is BRCA1 p.A1693_E1694delinsFILQ (this tells us that AE is deleted in the region 1693 and 1694, and FILQ is inserted).

 

SNV and indel variants are relevant for all cancer diseases and most targeted drugs.

 

One gene can have many SNVs and indels on it. Depending on how they change the gene, SNVs and indels can have either a strong effect or a minor effect on how the proteins function. A frameshift and a premature stop are examples of strong effects.

Changes that may affect an entire exon are called copy number alterations (CNA) or copy number variants (CNVs). An example of a CNV is BRCA1.Loss or BRCA1.Gain.

 

If two previously separate genes combine to form a new gene, this is called a fusion gene. An example of a fusion gene is ALK/EML4.

 

Each gene can only have one CNV or fusion on it. CNVs are relevant for breast, ovarian, and stomach cancers, and fusion genes are relevant for the cancer types lung, lymphoma, and leukemia.

Another category of genomic information are biomarkers, such as tumor mutational burden (TMB), or microsatellite instability (MSI), that do not occur per gene, they are measured once across an entire sample.

 

MSI can be MSI high or MSI stable, TMB can be TMB high or TMB low, Protein expression can be, for example, underexpression or overexpression.

 

Biomarkers such as MSI and TMB are relevant mostly for immunotherapy medication.

 

PD-L1 protein expression=HIGH is a strong indicator for success of immunotherapy.

The drugs for treating your cancer

The MH Guide report uses color coding to show whether a drug is likely to help against your cancer.

The biomarker score tells your physician whether the drug is approved.

Tier IA and Clinically approved 7 are the highest scores; they mean that the FDA has approved the drug for patients with your cancer and this variant.

For the approval, the evidence proving a drug’s effectiveness is considered, and also the medication costs. If a drug is approved, there is a good chance that it is reimbursed.

Explanations of medical and technical terms

An actionable variant or biomarker is a variant identified in a patient’s genetic test that makes the cancer grow and that can be targeted by a medicine known to be effective against that combination of variant and cancer.

These are the molecules used to build proteins. Protein are made of chains of amino acids, and the sequence of the amino acids is encoded in our genes.

A molecule that can be found in your body, for example, in your tumor or in your blood. Some biomarkers provide physicians with information about how patients with a specific disease will react to a specific drug. Testing for biomarkers is important for cancer patients. Also called variants, mutations, alterations, or gene defects.

This is a procedure by which your physician collects a small sample of cells from your cancer for testing in the lab. Depending on the cancer type, the cells are either taken from the tumor itself, or from bone marrow, or from skin. Samples from blood are only possible for blood cancers.

A segment of DNA or RNA, with information on how the amino acids of a protein are encoded. Most genes have multiple exons.

The study of heredity. If you are born with a cancer-causing gene variant inherited from your mother or father, you have a higher risk of developing cancer. This type of cancer is called hereditary cancer.

The study of genes and their functions. Cancer genomics studies the DNA of cancer cells compared to healthy cells.

Also called genomic tests, genomic profiling, genetic tests, or molecular diagnostics, are medical diagnostic tests that check whether variations (variants) are present in a person’s genetic code (genome) that tell physicians about the type of cancer they have and how their disease may react to specific drugs. This combination of gene and drug information is called biomarker, from biological + marker.

The basic building blocks of DNA and RNA.

Written by experts, using up-to-date evidence, they provide physicians with recommendations on the best care options.

Also called genomic tests, genomic profiling, genetic tests, or molecular diagnostics, are medical diagnostic tests that check whether variations (variants) are present in a person’s genetic code (genome) that tell physicians about the type of cancer they have and how their disease may react to specific drugs. This combination of gene and drug information is called biomarker, from biological + marker.

The median length of time patients are on a specific treatment before their cancer starts growing again.

Physicians use genomic diagnostic tests to find the medication that will work best for each patient.

The length of time patients are on a specific treatment and still alive.

A procedure by which tissue is surgically removed from your body, for example, to remove all or part of a tumor. Cells can then be collected from the tumor for testing in the lab.

The preparation and fixation of the sample for the lab. This is important for the accuracy of the interpretation of the genomic test results.

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Call us for a product demo or, if you are a patient, talk to your treating physician to see how you can benefit from an MH Guide analysis.

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