Popular Science | Frequently Asked Questions About Genetic Testing

Original title: Popular Science | Frequently Asked Questions about Genetic Testing

Genetic Test (Genetic Test) is based on chromosome structure, DNA sequence, DNA mutation site or gene expression level, and provides the basis for subjects and medical researchers to evaluate some diseases, constitutions or personal characteristics related to genetic inheritance It is also a method of precision medical analysis. Every person’s DNA genes are unique and personalized information, causing everyone’s innate physique, health status, and characteristics to be different. In 2008, the American Time magazine once referred to this revolution Sexual technology was selected as the Best Inovation of 2008 (Best Inovation of 2008).

Since the completion of the Human Genome Project in 2000, more and more gene functions have been successfully interpreted. Now more than 700 gene-related diseases have been developed with corresponding drugs and treatment methods. Including cancer and many rare diseases, the development and application of its drugs are ongoing. At present, the technology of genetic testing has gradually matured. In addition to the application of the detected genotypes in diagnosis and treatment, it can even predict the risk of disease that has not yet occurred based on the content of the database through digital statistics.

Application direction of genetic testing

• The main application directions of genetic testing include: identity verification/parent-child relationship verification/tracing ancestral origin
• Single gene/chromosomal genetic disease diagnosis and carrier screening
• Clinical preventive medicine: genetic testing for polygenic genetic diseases
• Clinical individualized medicine: Pharmacogenomics
• Congenital Physique/Trait Potential Analysis

With the rapid development of genetic testing technology, genetic testing has now been widely used in various fields of the medical industry, such as physical examination, cancer screening, cancer treatment, and so on. Do all cancer patients have to undergo genetic testing? Broadly speaking, all cancer patients can receive genetic testing; in a narrow sense, according to the guidelines recommended, different diseases, different stages, for different purposes, and different patients are suitable for different genetic testing.

1. What is tumor genetic testing?

Tumor gene detection is a technology to detect the DNA of tumor patients through tissues, blood, other body fluids or cells. The DNA molecular information in the cells of the subject is detected through specific testing equipment, and various genes contained in it are analyzed. In this way, the most suitable treatment plan can be tailored for each patient to maximize the effectiveness of treatment, reduce the toxic side effects of drugs, and prevent improper medication from delaying treatment opportunities. Tumor genetic testing is also the basis of tumor precision medicine.

2. What is the use of tumor genetic testing?

Tumor tissue or blood genetic testing is a very important part of evaluating the type of drugs used by patients and determining the effect. It can give doctors precise guidance on the use of drugs from the molecular level to achieve the effect of improving the efficacy and reducing side effects.

1) Choose the most effective tumor treatment drug;

2) Determine the therapeutic effect and drug resistance through continuous dynamic analysis of related genes;

3) Through the analysis of gene mutations and microsatellite stability, preliminary analysis of tumor burden (TMB) status is helpful to determine the effectiveness of immunotherapy drugs;

4) Detection of the status of related genes helps to understand the possible causes of tumors.

3. What is the tumor gene detection panel?

Panel is a term developed from NGS (next-generation sequencing, high-throughput sequencing technology) technology, which mainly refers to the simultaneous detection of multiple genes and multiple sites. Several genes can be a panel, dozens of genes can be a panel, and hundreds of genes can be a panel.Panel, combined together we call "gene package".

4. For tumor genetic testing, is the larger the panel, the better?

First of all, there are currently more than 3,000 genetic companies on the market, and some companies are unreliable and need to choose qualified and experienced companies. Secondly, when choosing products (large, medium and small panels), it is recommended that you choose according to economic conditions and patient conditions. For example, for a patient with advanced lung adenocarcinoma, the economic situation is average, just to see if there are suitable targeted drugs that have been marketed in the mainland are available, then just test the most common genes. For another example, a local tyrant wants to see if he has a targeted drug available: whether it is already on the market or in the clinical trial research stage, whether it is domestic or foreign, he wants to know. Then, he can choose to make as many genes as possible, dozens of hundreds or even all of them. PS: If you have the financial strength, it is recommended to make the package as large as possible. For example, when there are multiple metastases in the late stage, especially in patients with drug resistance, the gene mutations are more complicated and disordered. Check early to avoid treatment failure. The large package can also check PD-L1, TMB, MSI and MMR to see if it is suitable for immunotherapy.

5. If the pathological slices from two years ago are kept intact, can genetic testing be done, and how should the samples be selected?

Disease is evolving continuously, and the progress is relatively fast. If you want to know the current situation, it is best not to use case evidence from many years ago. The pathological slices two years ago cannot accurately reflect the truth. The current pathological state. Tumor gene detection sample priority order: new tissue samples/pleural and ascites samples taken from recent surgery or biopsy>tissue samples within 1-2 years>latest blood samples>old tissue samples more than 2 years old.

6. Issues regarding the sample size and sample storage.

Fresh surgical tissue: the size of soybeans, it is recommended to use the tissue preservation solution dedicated to the laboratory; formalin is not recommended. If only formalin is used, the inspection form must be clearly marked, and the laboratory will arrange specific The extraction method.

To puncture the tissue, you need 3 fine needles and 1 thick needle.

White slices: It is recommended that about 15 slices of NGS samples. About 5 pieces for PCR or IHC.

If the sample size is not enough or does not meet the requirements, the inspection institute will request subsequent replenishment.

7. Why is the treatment of Iressa effective in patients with EGFR-negative adenocarcinoma?

There are several situations that may lead to this result:

1) The sensitivity of the detection method is different, is it ARMS-PCR or NGS? NGS has higher sensitivity;

2) The patient's mutation abundance is relatively low, and the routine sensitivity test will have a negative result, but the low-abundance mutation is also effective for the treatment of TKI;

3) Rare mutations. At present, about 200 EGFR mutation methods have been discovered, but the clinically common detection methods only cover the most common 29. Some of the remaining rare mutations are effective for TKI;

4) There is a difference between the specimens submitted for inspection, blood test or tissue biopsy test, if it is a blood biopsy, there may be a certain false negative;

5) The tumor tissue is heterogeneous, and the biopsy tissue is just negative for EGFR expression.

8. What is tumor immunotherapy?

Under normal circumstances, the immune system can recognize and remove tumor cells in the tumor microenvironment, but in order to survive and grow, tumor cells can adopt different strategies to suppress the body’s immune system and not normally kill tumor cells. All stages of the anti-tumor immune response survived.

Tumor immunotherapy is a treatment method that restores the body's normal anti-tumor immune response by restarting and maintaining the tumor-immune cycle, thereby controlling and eliminating tumors.Including drug immunotherapy and cellular immunotherapy.

9. What are the tumor immunotherapy drugs?

According to whether the treatment is specific to tumor cells or tissues, we divide drug immunotherapy into two parts: non-specific and specific drug immunotherapy. Non-specific drug immunotherapy does not have a specific immune cell target. It is a drug that improves human immunity as a whole to relieve tumor symptoms. It is also called an immunomodulator, such as domestic thymopentin and Chinese medicine immunotherapy drugs; specific drugs It has clear targets and mechanisms that can activate or inhibit clear targets to achieve immune activation of the immune system to tumors, such as immune checkpoint inhibitors (PD-1/PD-L1 antibody drugs). The PD-1/PD-L1 inhibitors currently approved by the FDA are listed in the table below. Currently, pharmaceutical companies are conducting clinical trials in many domestic tertiary hospitals and provide enrollment quotas (need to meet entry requirements).

10. Is there any correlation between the immune checkpoint inhibitor targets PDL1, TMB, MSI, MMR and other targets?

PD1/PDL1 is a classic marker, but its specificity is low, the detection is subject to many interference factors, and the expression rate is low in digestive tract tumors, which makes it not a good predictive marker for immune checkpoint inhibitors. TMB can evaluate the effectiveness of nearly 55% of tumor immunotherapy and is a potential good marker in the future. MSI/MMR is approved by the FDA for all solid tumor immune checkpoint inhibitor medication guidance; MSI itself is a form of tumor mutation burden, and MSI-H indicates the presence of high TMB in this tumor. There is no conflict between TMB and PD1/PDL1, and the combination of the two can more effectively predict the efficacy of immune drugs, so it can be jointly tested.

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